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  • 1.
    Bao, Xue
    et al.
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China;Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Borne, Yan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Muhammad, Iram Faqir
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Nilsson, Jan
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Melander, Olle
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Niu, Kaijun
    Tianjin Med Univ, Nutr Epidemiol Inst, Tianjin, Peoples R China;Tianjin Med Univ, Sch Publ Hlth, Tianjin, Peoples R China.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, CRC, Jan Waldenstroms Gata 35,Hus 60 Plan 13, S-20502 Malmo, Sweden.
    Growth differentiation factor 15 is positively associated with incidence of diabetes mellitus: the Malmö Diet and Cancer-Cardiovascular Cohort2019In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 1, p. 78-86Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Growth differentiation factor 15 (GDF-15) is an anti-inflammatory cytokine of the transforming growth factor- superfamily. Circulating levels of GDF-15 are associated with hyperglycaemia among people with obesity or diabetes, but longitudinal evidence on the association between GDF-15 levels and diabetes risk is scarce. Our aim was to explore whether circulating levels of GDF-15 at baseline are positively associated with future diabetes incidence in a middle-aged urban population.

    Methods: Between 1991 and 1994, baseline fasting plasma GDF-15 levels were measured in 4360 individuals without diabetes (mean age 57.45.96years, 38.6% men) who were participants in the Malmo Diet and Cancer-Cardiovascular Cohort. After a follow-up of 19.05.16years (mean +/- SD), Cox proportional hazards regression analysis was used for the study of the relationship between baseline GDF-15 and incident diabetes, with adjustment for established confounders. A sensitivity analysis included further adjustment for levels of C-reactive protein (CRP).

    Results: During the follow-up period, 621 individuals developed diabetes. The multivariate-adjusted HR for diabetes incidence was 1.43 (95% CI 1.11, 1.83; p for trend = 0.007) for the fourth compared with the first quartile of GDF-15, and was 1.17 (95% CI 1.07, 1.28; p<0.001) per SD increase of GDF-15. If participants were grouped according to baseline fasting glucose, the association between GDF-15 and diabetes risk was only evident in the group without impaired fasting glucose (n=3973). The association tended to be less significant with increasing age: multivariate-adjusted HRs for diabetes per SD increase of GDF-15 were 1.24 (95% CI 1.08, 1.42), 1.19 (95% CI 1.00, 1.41) and 1.04 (95% CI 0.89, 1.23) for participants aged 55, 56-60 (>55 and 60) and >60years, respectively. With adjustment for levels of CRP, the HR per SD increase of GDF-15 (1.21, 95% CI 1.09, 1.35) was significant (p=0.015), but the HR for the fourth compared with the first quartile of GDF-15 was not significant (HR 1.30; 95% CI 1.01, 1.67; p for trend = 0.061).

    Conclusions/interpretation: GDF-15 may be useful for identification of people with a risk of incident diabetes, especially if those people are 60years old.

  • 2.
    Beijer, Kristina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nilsson, Peter M.
    SUS Malmö, Dept Clin Sci, Malmö, Sweden.
    Elmståhl, Sölve
    Lund Univ, Malmö Univ Hosp, Dept Hlth Sci, Div Geriatr Med, Malmö, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Physical activity may compensate for prolonged TV time regarding pulse rate-a cross-sectional study2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Background: Regular exercise reduces pulse rate, but it is less clear how prolonged sitting time affects pulse rate. Our hypothesis was that high physical activity could compensate for prolonged sitting time regarding the pulse rate.

    Methods: Regression analysis was performed on cross-sectional data including 47,457 men and women based on two Swedish cohort studies, EpiHealth (18–45 years) and LifeGene (45–75 years). Self-reported leisure time physical activity was given in five levels, from low (level 1) to vigorous (level 5), and television time was used as a proxy of sitting time.

    Results: A higher physical activity (level 4 compared to level 1) was associated with a lower pulse rate in middle-aged females (-2.7 beats per minute [bpm]; 95% CI -3.3 to -2.2) and males (-4.0 bpm; 95% CI -4.7 to -3.4). The relationship between physical activity and pulse rate was strongest in the young. A prolonged television time (3 h compared to 1 h per day) was associated with a slightly higher pulse rate in middle-aged females (+0.6 bpm; 95% CI +0.3 to +0.8) and males (+0.9 bpm; 95% CI +0.7 to +1.2). Among participants with a prolonged television time (3 h), those with a high physical activity (level 4) had a lower pulse rate compared to those with a low physical activity (level 1).

    Conclusions: A prolonged television time was associated with a high pulse rate, while high physical activity was associated with a low pulse rate. The results suggest that a high physical activity could compensate for a prolonged television time regarding pulse rate.

  • 3.
    Berglund, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Westerling, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Length of time periods in treatment effect descriptions and willingness to initiate preventive therapy: a randomised survey experiment2018In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 18, article id 106Article in journal (Refereed)
    Abstract [en]

    Background Common measures used to describe preventive treatment effects today are proportional, i.e. they compare the proportions of events in relative or absolute terms, however they are not easily interpreted from the patient's perspective and different magnitudes do not seem to clearly discriminate between levels of effect presented to people. Methods In this randomised cross-sectional survey experiment, performed in a Swedish population-based sample (n=1041, response rate 58.6%), the respondents, aged between 40 and 75years were given information on a hypothetical preventive cardiovascular treatment. Respondents were randomised into groups in which the treatment was described as having the effect of delaying a heart attack for different periods of time (Delay of Event,DoE): 1month, 6months or 18months. Respondents were thereafter asked about their willingness to initiate such therapy, as well as questions about how they valued the proposed therapy. ResultsLonger DoE:s were associated with comparatively greater willingness to initiate treatment. The proportions accepting treatment were 81, 71 and 46% when postponement was 18months, 6months and 1month respectively. In adjusted binary logistic regression models the odds ratio for being willing to take therapy was 4.45 (95% CI 2.72-7.30) for a DoE of 6months, and 6.08 (95% CI 3.61-10.23) for a DoE of 18months compared with a DoE of 1month. Greater belief in the necessity of medical treatment increased the odds of being willing to initiate therapy. ConclusionsLay people's willingness to initiate preventive therapy was sensitive to the magnitude of the effect presented as DoE. The results indicate that DoE is a comprehensible effect measure, of potential value in shared clinical decision-making.

  • 4.
    Bixby, Honor
    et al.
    Imperial College London, London, UK.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yngve, Agneta
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Ezzati, Majid
    Imperial College London, London, UK.
    Rising rural body-mass index is the main driver of the global obesity epidemic in adults2019In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 569, no 7755, p. 260-264Article in journal (Other academic)
    Abstract [en]

    Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

  • 5.
    Cai, Gui-Hong
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Elmstahl, S.
    Lund Univ, Div Geriatr Med, Dept Hlth Sci, Lund, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Both weight at age 20 and weight gain have an impact on sleep disturbances later in life – results of the epihealth study2017In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 40, no Supplement 1, p. E195-E195Article in journal (Other academic)
  • 6.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    A framework for monitoring of new drugs in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

  • 7.
    Chróinín, Danielle Ní
    et al.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Asplund, Kjell
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Callaly, Elizabeth
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Cuadrado-Godia, Elisa
    Hosp del Mar IMIM, Dept Neurol, Barcelona, Spain.
    Diez-Tejedor, Exuperio
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Di Napoli, Mario
    San Camillo deLellis Gen Hosp, Neurol Serv, Rieti, Italy; Ctr Cardiovasc Med & Cerebrovasc Dis Prevent, SMDN, Laquila, Italy .
    Engelter, Stefan T.
    Univ Basel Hosp, Dept Neurol, Basel, Switzerland.
    Furie, Karen L.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Giannopoulos, Sotirios
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Gotto, Antonio M., Jr.
    Weill Cornell Med Coll, New York, NY USA.
    Hannon, Niamh
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Jonsson, Fredrik
    Umeå Univ Hosp, Dept Med, Umeå, Sweden.
    Kapral, Moira K.
    Toronto Gen Hosp, Inst Clin Evaluat Sci, Toronto, ON, Canada.
    Martí-Fàbregas, Joan
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Martínez-Sánchez, Patricia
    Univ Autonoma Madrid, Dept Neurol, La Paz Univ Hosp, Madrid, Spain; Univ Autonoma Madrid, Stroke Ctr, La Paz Univ Hosp, Madrid, Spain.
    Milionis, Haralampos J.
    Univ Ioannina, Sch Med, Ioannina, Greece.
    Montaner, Joan
    Autonomous Univ Barcelona, Hosp Vall dHebron, Barcelona, Spain; Autonomous Univ Barcelona, Vall dHebron Res Inst VHIR, Barcelona, Spain.
    Muscari, Antonio
    Univ Bologna, S Orsola Malpighi Hosp, Bologna, Italy.
    Pikija, Slaven
    Gen Hosp Varazdin, Varazhdin, Croatia.
    Probstfield, Jeffrey
    Univ Washington, Dept Med, Seattle, WA USA; Univ Washington, Dept Epidemiol, Seattle, WA USA.
    Rost, Natalia S.
    Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Ctr Human Genet Res, Boston, MA USA.
    Thrift, Amanda G.
    Monash Univ, Monash Med Ctr, Stroke & Ageing Res Ctr, Dept Med, Clayton, Vic, Australia; Natl Stroke Res Inst, Heidelberg, Vic, Australia.
    Vemmos, Konstantinos
    Univ Athens, Dept Therapeut, Alexandra Hosp, Athens, Greece.
    Kelly, Peter J.
    Natl Univ Ireland Univ Coll Dublin, Neurovasc Unit Appl Translat Res & Therapeut, Mater Univ Hosp, Dublin Acad Med Ctr, Dublin, Ireland.
    Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 2, p. 448-456Article, review/survey (Refereed)
    Abstract [en]

    Background and Purpose: Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke.

    Methods: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients.

    Results: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29–1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9–1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62–0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67–0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0–2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02–1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90–1.44; 4012 patients).

    Conclusion: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  • 8.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 9.
    Dumanski, Jan P.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab. Faculty of Pharmacy, Medical University of Gdansk, Poland.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Forsberg, Lars A.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Beijer Laboratory of Genome Research, Uppsala University.
    Loss of Chromosome Y in Leukocytes and Major Cardiovascular Events2017In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, no 4Article in journal (Other academic)
  • 10.
    Feo, Rebecca
    et al.
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia;Flinders Univ S Australia, Coll Nursing & Hlth Sci, Adelaide, SA, Australia.
    Donnelly, Frank
    Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Jangland, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Providing high-quality fundamental care for patients with acute abdominal pain: A qualitative study of patients' experiences in acute care2019In: Journal of Health Organisation & Management, ISSN 1477-7266, E-ISSN 1758-7247, Vol. 33, no 1, p. 110-123Article in journal (Refereed)
    Abstract [en]

    Purpose Globally, acute abdominal pain (AAP) is one of the most common reasons for emergency admissions, yet little is known about how this patient group experiences the delivery of fundamental care across the acute care delivery chain. The purpose of this paper is to describe how patients with AAP experienced fundamental care across their acute care presentation, and to explicate the health professional behaviours, reported by patients, that contributed to their positive experiences. Design/methodology/approach A qualitative descriptive study, using repeated reflective interviews, was analysed thematically (n=10 patients). Findings Two themes were identified: developing genuine, caring relationships with health professionals and being informed about one's care. Patients reported that health professionals established genuine professional-patient relationships despite the busy care environment but perceived this environment as impeding information-provision. Patients were typically accepting of a lack of information, whereas poor professional-patient relationships were seen as inexcusable.

  • 11.
    Franceschini, Nora
    et al.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Giambartolomei, Claudia
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
    de Vries, Paul S.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Huntley, Rachael P.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Lovering, Ruth C.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93053 Regensburg, Germany.
    Graff, Misa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Dale, Caroline
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria;Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
    van Leeuwen, Elisabeth M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Lu, Lingyi
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Pitkanen, Niina
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland.
    Franzen, Oscar
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands.
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland.
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Framingham, MA 01702 USA;NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA.
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, D-17475 Greifswald, Germany.
    Palmas, Walter
    Columbia Univ, Dept Med, New York, NY 10032 USA.
    Isaacs, Aaron
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Maastricht Univ, CARIM Sch Cardiovasc Dis, Maastricht Ctr Syst Biol MaCSBio, Dept Biochem, NL-6229 Maastricht, Netherlands.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 25157 USA;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld 4222, Australia.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Wong, Andrew
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Smit, Andries J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Med, NL-2300 Groningen, Netherlands.
    Newman, Anne B.
    Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA;Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
    Britton, Annie
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Ruusalepp, Arno
    Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, EE-51010 Tartu, Estonia.
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Hedblad, Bo
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Pasaniuc, Bogdan
    Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA;Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
    Penninx, Brenda W.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res & Neurosci Campus Amste, Department Psychiat, NL-1081 HL Amsterdam, Netherlands.
    Langefeld, Carl D.
    Wake Forest Univ, Bowman Gray Sch Med, Dept Biostatist Sci, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Wassel, Christina L.
    Premier Inc, Appl Sci, Charlotte, NC 28277 USA.
    Tzourio, Christophe
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Fava, Cristiano
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden;Univ Verona, Dept Med, I-37134 Verona, Italy.
    Baldassarre, Damiano
    Univ Milan, Dept Med Biotechnol & Translat Med, I-20133 Milan, Italy;IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    O'Leary, Daniel H.
    Tufts Univ, Sch Med, St Elizabeths Med Ctr, Boston, MA 02135 USA.
    Teupser, Daniel
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Kuh, Diana
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Tremoli, Elena
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy;Univ Milan, Dipartimento Sci Farmacol Biomol, I-20133 Milan, Italy.
    Mannarino, Elmo
    Univ Perugia, Internal Med Angiol & Arteriosclerosis Dis, Dept Clin & Expt Med, I-06123 Perugia, Italy.
    Grossi, Enzo
    Ctr Diagnost Italiano, I-20147 Milan, Italy.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94309 USA;Stanford Univ, Stanford Cardiovasc Inst, G1120, Stanford, CA USA.
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, I-20138 Milan, Italy.
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus Med Ctr, Dept Internal Med, NL-3015 Rotterdam, Netherlands.
    Beutner, Frank
    Heart Ctr Leipzig, D-04103 Leipzig, Germany.
    Chauhan, Ganesh
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France;Indian Inst Sci, Ctr Brain Res, Bangalore 560012, Karnataka, India.
    Heiss, Gerardo
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-3015 Groningen, Netherlands.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.
    Markus, Hugh S.
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands.
    Price, Jacqueline
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Pott, Janne
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Liang, Jingjing
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany.
    Engmann, Jorgen
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98105 USA.
    Taylor, Kent D.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Dhana, Klodian
    Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA.
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27516 USA.
    Launer, Lenore J.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Holdt, Lesca M.
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;LMU, Univ Hosp Munich, Inst Lab Med, D-80539 Munich, Germany.
    Doer, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, D-17475 Greifswald, Germany.
    Dichgans, Martin
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany;Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany.
    Traylor, Matthew
    Univ Cambridge, Dept Clin Neurosci, Stroke Res Grp, Cambridge CB2 0QQ, England.
    Sitzer, Matthias
    Goethe Univ Frankfurt, Ctr Neurol & Neurosurg, Dept Neurol, D-60323 Frankfurt, Germany.
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England;Essex Univ, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England.
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden.
    Raitakari, Olli
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Bern, ISPM, CH-3012 Bern, Switzerland.
    Rueda-Ochoa, Oscar L.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Ind Santander, Sch Med, Electrocardiog Res Grp, Santander 680003, Colombia.
    Roussos, Panos
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA;James J Peters VA Med Ctr, MIRECC, Bronx, NY 10468 USA.
    Whincup, Peter H.
    St Georges Univ London, Populat Hlth Res Inst, London SW17 0RE, England.
    Amouyel, Philippe
    INSERM, U1167, F-59000 Lille, France;Inst Pasteur, U1167, F-59000 Lille, France;Univ Lille, U1167, RID AGE, F-59000 Lille, France;CHU Lille, U1167, F-59000 Lille, France.
    Giral, Philippe
    Sorbonne Univ, Pitie Salpetriere Hosp, Cardiovasc Prevent Unit, F-75013 Paris, France.
    Anugu, Pramod
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
    Wong, Quenna
    Univ Washington, Dept Biostat, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
    Malik, Rainer
    LMU, Univ Hosp, Inst Stroke & Dementia Res ISD, D-80539 Munich, Germany.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany;Univ Leipzig, Inst Lab Med, D-04109 Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, D-93053 Regensburg, Germany.
    Hardy, Rebecca
    UCL, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, A-8036 Graz, Austria.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands.
    Morris, Richard W.
    Univ Bristol, Bristol Med Sch, Dept Populat Hlth Sci, Bristol BS8 1QU, Avon, England.
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden;Univ Glasgow, Inst Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow G12 0XH, Lanark, Scotland.
    Wannamethee, S. Goya
    UCL, Dept Primary Care & Populat Hlth, London WC1E 6BT, England.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
    Shah, Sonia
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    McLachlan, Stela
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, NL-2300 RC Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, FI-70210 Kuopio, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA.
    Ring, Susan
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 GA Nijmegen, Netherlands.
    Shah, Tina
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, S-17177 Stockholm, Sweden.
    Plagnol, Vincent
    UCL, Genet Inst, London WC1E 6BT, England.
    Rosamond, Wayne D.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27516 USA.
    Post, Wendy
    Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA;Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA.
    Zhu, Xiaofeng
    Case Western Reserve Univ, Sch Med, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA.
    Zhang, Xiaoling
    NHLBI, Intramural Res Program, Framingham Heart Study, Framingham, MA 01702 USA;Boston Univ, Sch Med, Sect Biomed Genet, Boston, MA 02215 USA.
    Guo, Xiuqing
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London SW7 2AZ, England.
    Seldenrijk, Adrie
    Univ Amsterdam, Med Ctr, Dept Psychiat, GGZ inGeest & Amsterdam Publ Hlth Res Inst, NL-1081 HV Amsterdam, Netherlands.
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA.
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17177 Stockholm, Sweden.
    Psaty, Bruce M.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA;Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 Rotterdam, Netherlands;Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford OX3 7LF, England.
    Lawlor, Deborah A.
    Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol BS8 1QU, Avon, England;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 1TH, Avon, England.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2333 ZA Leiden, Netherlands.
    Bowden, Donald W.
    Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Gen, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, A-8010 Graz, Austria.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA;Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Dept Pediat, Med Ctr, Torrance, CA 90502 USA.
    Wardlaw, Joanna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland;Univ Edinburgh, UK Dementia Res Inst, Edinburgh EH16 4SB, Midlothian, Scotland.
    Deanfield, John
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Halcox, Julian
    Swansea Univ, Med Sch, Swansea SA2 8PP, W Glam, Wales.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33014, Finland;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, D-04107 Leipzig, Germany.
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Debette, Stephanie
    Univ Bordeaux, INSERM, CHU Bordeaux, Bordeaux Populat Hlth Res Ctr,UMR 1219, F-33000 Bordeaux, France.
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Crt Cardiovasc Genet, London WC1E 6BT, England.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Gen, D-17475 Greifswald, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland;Univ Iceland, IS-101 Reykjavik, Iceland.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
    Bjorkegren, Johan L. M.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Clin Gene Networks AB, S-10462 Stockholm, Sweden;Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, EE-51010 Tartu, Estonia;Karolinska Univ Sjukhuset, Karolinska Inst, Dept Med, Integrated Cardio Metab Ctr, SE-14157 Huddinge, Sweden.
    Casas, Juan P.
    UCL, Inst Hlth Informat, London WC1E 6BT, England.
    O'Donnell, Christopher J.
    NHLBI, Intramural Adm Management Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02130 USA;Harvard Med Sch, Boston, MA 02115 USA.
    GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 5141Article in journal (Refereed)
    Abstract [en]

    Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.

  • 12.
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    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Childrens Hosp Eastern Ontario, NSO, Ottawa, ON, Canada.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Humanities & Sci, Dept Biol, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
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    Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
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    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
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    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA.
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    Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA.
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
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    Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
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    Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA;Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21218 USA.
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    Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Biomed Data Sci, Stanford, CA 94305 USA.
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    Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA;Stanford Univ, Stanford Ctr Undiagnosed Dis, Stanford, CA USA;Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
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    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Stanford Med Clin Genom Program, Stanford, CA 94305 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA;Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27515 USA;NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
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    Webb-Robertson, Bobbie-Jo M.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Westerfield, Monte
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wise, Anastasia L.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Wolfe, Lynne A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Worthey, Elizabeth A.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yamamoto, Shinya
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, John
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yang, Yaping
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yoon, Amanda J.
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Yu, Guoyun
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zhao, Chunli
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Zheng, Allison
    NIH, Undiagnosed Dis Network, Bldg 10, Bethesda, MD 20892 USA.
    Boycott, Kym
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    MacKenzie, Alex
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Majewski, Jacek
    McGill Univ, Montreal, PQ, Canada.
    Brudno, Michael
    Univ Toronto, Toronto, ON, Canada.
    Bulman, Dennis
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Dyment, David
    Univ Ottawa, Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
    Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts2019In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 6, p. 911-919Article in journal (Refereed)
    Abstract [en]

    It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.

  • 13.
    Jangland, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Teodorsson, Therese
    Hoglandssjukhuset Eksjo, Dept Surg, Eksjo, Sweden.
    Molander, Karin
    Sundsvall Hosp, Dept Surg, Sundsvall, Sweden.
    Muntlin Athlin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Health Services Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Univ Adelaide, Adelaide Nursing Sch, Adelaide, SA, Australia.
    Inadequate environment, resources, and values lead to missed nursing care: A focused ethnographic study on the surgical ward using the Fundamentals of Care framework2018In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 27, no 11-12, p. 2311-2321Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES: The purpose was to explore the delivery of care from the perspective of patients with acute abdominal pain focusing on the contextual factors at system level using the Fundamentals of Care framework.

    BACKGROUND: The Fundamentals of Care framework describes several contextual and systemic factors that can impact the delivery of care. To deliver high- quality, person-centred care it is important to understand how these factors affect patients' experiences and care needs.

    DESIGN: A focused ethnographic approach.

    METHOD: A total of 20 observations were performed on two surgical wards at a Swedish university hospital. Data were collected using participant observation and informal interviews and analysed using deductive content analysis.

    RESULTS: The findings, presented in four categories, reflect the value patients place on the caring relationship and a friendly atmosphere on the ward. Patients had concerns about the environment, particularly the high-tempo culture on the ward and its impact on their integrity, rest and sleep, access to information and planning, and need for support in addressing their existential thoughts. The observers also noted that missed nursing care had serious consequences for patient safety.

    CONCLUSION: Patients with acute abdominal pain were cared for in the high-tempo culture of a surgical ward with limited resources, unclear leadership, and challenges to patients' safety. The findings highlight the crucial importance of prioritizing and valuing the patients' fundamental care needs for recovery.

    RELEVANCE TO CLINICAL PRACTICE: Nursing leaders and nurses need to take the lead to re-conceptualize the value of fundamental care in the acute care setting. To improve clinical practice the value of fundamentals of care must be addressed regardless of patient's clinical condition. Providing a caring relationship is paramount to ensure a positive impact on patient's well-being and recovery.

  • 14. Justice, Anne E.
    et al.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindgren, Cecilia M.
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 452-469Article in journal (Refereed)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 15.
    Karasik, David
    et al.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Bar Ilan Univ, Azrieli Fac Med, Safed, Israel.
    Zillikens, M. Carola
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Hsu, Yi-Hsiang
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Akesson, Kristina
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden;Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;NIHR Cambridge Biomed Res Ctr, Cambridge, England;Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge, England.
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Lubeck, Germany.
    Bochud, Murielle
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland.
    Borecki, Ingrid B.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA;Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Campos-Obando, Natalia
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Chambers, John C.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Imperial Coll Healthcare NHS Trust, London, England;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London, England;Imperial Coll London, London, England.
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA.
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon, South Korea.
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea;Seoul Natl Univ, Coll Med, Neurosci Res Inst, Dept Anat & Cell Biol, Seoul, South Korea;Seoul Natl Univ, Wide River Inst Immunol, Hongcheon, South Korea.
    Chou, Wen-Chi
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Broad Inst, Cambridge, MA USA.
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    de Groot, Lisette C. P. G. M.
    Columbia Univ, Med Ctr, Ctr Translat & Computat Neuroimmunol Neurol, New York, NY USA.
    De Jager, Phillip L.
    Broad Inst, Cell Circuits Program, Cambridge, MA USA;Free Univ Berlin, Humboldt Univ Berlin, Charite Univ Med Berlin, Berlin, Germany.
    Demuth, Ilja
    Berlin Inst Hlth, Berlin, Germany;Wageningen Univ, Div Human Nutr, AFSG, Wageningen, Netherlands.
    Diatchenko, Luda
    Univ North Carolina Chapel Hill, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC USA;McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada.
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland.
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Eriksson, Johan G.
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland;Helsinki Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Estrada, Karol
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Biogen Inc, Translat Biol, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Feitosa, Mary F.
    Washington Univ, Dept Genet, Div Stat Gen, Sch Med, St Louis, MO 63110 USA.
    Fu, Mao
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Helmholtz Zentrum Munchen, CCG Type 2 Diabet, Neuherberg, Germany;German Ctr Diabet Res, Neuherberg, Germany.
    Gudnason, Vilmundur
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Lenore, Launer J.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, IGMM, Edinburgh, Midlothian, Scotland.
    Hofman, Albert
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
    Huffman, Kim M.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC 27706 USA;Duke Univ, Sch Med, Dept Med, Div Rheumatol, Durham, NC 27706 USA.
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Illig, Thomas
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Dept Human Genet, Hannover, Germany.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA USA.
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Jansson, John-Olov
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden.
    Johnson, Toby
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Univ Lausanne, Dept Med Genet, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Biffar, Reiner
    Ernst Moritz Arndt Univ Greifswald, Dept Prosthet Dent Gerodontol & Biomat, Ctr Oral Hlth, Greifswald, Germany.
    Jordan, Joanne M.
    Univ North Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chapel Hill, NC USA.
    Jula, Antti
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Karlsson, Magnus
    Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Kilpelainen, Tuomas O.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England;Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Klopp, Norman
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Koller, Daniel L.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Hammersmith Hosp, Natl Heart & Lung Inst Cardiovasc Sci, Fac Med, Hammersmith Campus, London, England.
    Kraus, William E.
    Duke Univ, Sch Med, Dept Med, Duke Mol Physiol Inst, Durham, NC USA;Duke Univ, Sch Med, Dept Med, Div Cardiol, Durham, NC USA.
    Kritchevsky, Stephen
    Wake Forest Sch Med, Sticht Ctr Hlth Aging & Alzheimers Prevent, Winston Salem, NC USA.
    Kutalik, Zoltan
    Lausanne Univ Hosp, Univ Inst Social & Prevent Med, Lausanne, Switzerland;Helmholtz Zentrum Munchen, CCG Nutrigen & Type 2 Diabet, Neuherberg, Germany;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Lahti, Jari
    Univ Helsinki, Helsinki Collegium Adv Studies, Helsinki, Finland.
    Lang, Thomas
    UC San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA USA;UC San Francisco, Sch Dent, San Francisco, CA USA.
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Childrens Hosp Westmead,Ctr Kidney Res, Sydney, NSW, Australia.
    Lill, Christina
    Univ Lubeck, Inst Neurogenet, Lubeck, Germany.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Livshits, Gregory
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, Gothenburg, Sweden.
    Luan, Jian'an
    Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY USA.
    Luben, Robert N.
    Univ Copenhagen, Fac Hlth & Med Sci, Sect Metabol Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Malkin, Ida
    Tel Aviv Univ, Dept Anat & Anthropol, Sackler Fac Med, Tel Aviv, Israel.
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, Munich, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, Neuherberg, Germany.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England.
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, Aarhus, Denmark.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Newman, Anne B.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    O'Connell, Jeffery R.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Palotie, Aarno
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Dept Med Genet, Helsinki, Finland;Univ Cent Hosp, Helsinki, Finland.
    Peacock, Munro
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
    Perola, Markus
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med, Helsinki, Finland;Diabet & Obes Res Program, Helsinki, Finland;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany.
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    Raikkonen, Katri
    Univ Helsinki, Dept Psychol & Logoped, Helsinki, Finland.
    Ralston, Stuart H.
    Harvard Med Sch, Boston, MA 02115 USA;Western Gen Hosp, MRC Inst Genet & Mol Med, Mol Med Ctr, Edinburgh, Midlothian, Scotland.
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland;Univ Helsinki, Hjelt Inst, Helsinki, Finland.
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
    Rudan, Igor
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welfare, Helsinki, Finland.
    Satterfield, Suzanne
    Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
    Smith, Albert V.
    Iceland Heart Assoc Holtasmari, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Smith, Shad B.
    Duke Univ, Dept Anesthesiol, Ctr Translat Pain Med, Durham, NC USA.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Steinhagen-Thiessen, Elisabeth
    Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
    Streeten, Elizabeth A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
    Styrkarsdottir, Unnur
    deCODE Genet, Reykjavik, Iceland.
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Thompson, Patricia
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ USA;SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA.
    Thomson, Cynthia A.
    Thorleifsson, Gudmar
    deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet, Reykjavik, Iceland.
    Tikkanen, Emmi
    Natl Inst Hlth & Welfare, Helsinki, Finland;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Ctr Med Syst Biol & Netherlands Consortium H, Leiden, Netherlands.
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands;Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Vollenweider, Peter
    Lausanne Univ Hosp, Dept Med Internal Med, Lausanne, Switzerland;Fac Biol & Med, Lausanne, Switzerland.
    Volzke, Henry
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Wactawski-Wende, Jean
    Univ Buffalo SUNY, Dept Epidemiol & Environm Hlth, Buffalo, NY USA.
    Walker, Mark
    Newcastle Univ, Med Sch, Inst Cellular Med Diabetes, Framlington Pl, Newcastle Upon Tyne, Tyne & Wear, England.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Waterworth, Dawn
    GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Weedon, Michael N.
    Univ Exeter, Med Sch, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter, Devon, England.
    Wichmann, H-Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Neuherberg, Germany;Tech Univ, Inst Med Stat & Epidemiol, Munich, Germany.
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London, England.
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Teviot Pl, Edinburgh, Midlothian, Scotland.
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized & Genom Med, Baltimore, MD 21201 USA;Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA;GlaxoSmithKline, Genet, King Of Prussia, PA USA.
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
    Zhang, Weihua
    Ealing Hosp NHS Trust, Cardiol, London, England;Imperial Coll Healthcare NHS Trust, London, England.
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge Biomed Campus, Cambridge, England.
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR USA.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, Bethesda, MD 20892 USA.
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Kiel, Douglas P.
    Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
    Disentangling the genetics of lean mass2019In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 276-287Article in journal (Refereed)
    Abstract [en]

    Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age(2), and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LMwere termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

  • 16.
    Larsson, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden.
    Farahmand, Bahman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Zelano, J.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden.
    Risk of Stroke after Late-Onset Seizures: A Swedish Register-Based Case-Control Study2018In: Epilepsia, ISSN 0013-9580, E-ISSN 1528-1167, Vol. 59, p. S5-S6Article in journal (Other academic)
  • 17.
    Larsson, David
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden; Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Zelano, Johan
    Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden; Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Retention rate of first antiepileptic drug in poststroke epilepsy: A nationwide study2019In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 64, p. 29-33Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the retention rates of first antiepileptic drugs (AEDs) in patients with poststroke epilepsy on a nationwide scale.

    Methods: The Swedish Stroke Register, which has 94% coverage and high-resolution data on stroke, comorbidities, and disability, was cross-referenced to the National Patient Register, Drug Register, and Cause-of-Death Register. Patients with onset of AED-treated epilepsy after stroke in 2005–2010 were included. An algorithm based on prescription renewal intervals was used to analyze treatment data until the end of 2014.

    Results: A total of 4991 patients were included. First AEDs analyzed were carbamazepine (n = 2373), valproic acid (n = 943), levetiracetam (n = 555), lamotrigine (n = 519), phenytoin (n = 176), and oxcarbazepine (n = 89). The five-year retention rate was highest for lamotrigine (75%, 95%CI:70.4–79.4), followed by levetiracetam (69%, 95%CI:62.9–74.3), oxcarbazepine (68%, 95%CI:55.2–79.8), valproic acid (62%, 95%CI:57.8–66.4), carbamazepine (60%, 95%CI:57.6–62.4), and phenytoin (55%, 95%CI:45.2–64.0). There were minor differences in baseline characteristics with low levels of disability being slightly more common in patients treated with lamotrigine and levetiracetam. Atrial fibrillation and hypertension were more common in patients treated with levetiracetam, and atrial fibrillation was less common in patients treated with carbamazepine. In a Cox model adjusted for baseline characteristics, the risk of discontinuation was lower for lamotrigine (HR 0.53, 95%CI:0.43-0.67) and levetiracetam (HR 0.75, 95%CI:0.60-0.94) when compared to carbamazepine.

    Conclusions: Lamotrigine and levetiracetam have higher retention rates than carbamazepine in poststroke epilepsy. This is in agreement with existing small RCTs in this patient group.

  • 18.
    Laszkowska, M.
    et al.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Mahadev, S.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lebwohl, B.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Green, P. H. R.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ludvigsson, J. F.
    Columbia Univ Coll Phys & Surg, Dept Med, Celiac Dis Ctr, New York, NY USA;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden;Orebro Univ Hosp, Dept Paediat, Orebro, Sweden;Univ Nottingham, Sch Med, Div Epidemiol & Publ Hlth, Nottingham, England.
    Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis2018In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 6, p. 590-597Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis.

    AIMS: To investigate the prevalence of CD among individuals with osteoporosis.

    METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression.

    RESULTS:  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%).

    CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

  • 19. Ligthart, Symen
    et al.
    Vaez, Ahmad
    Võsa, Urmo
    Stathopoulou, Maria G
    de Vries, Paul S
    Prins, Bram P
    Van der Most, Peter J
    Tanaka, Toshiko
    Naderi, Elnaz
    Rose, Lynda M
    Wu, Ying
    Karlsson, Robert
    Barbalic, Maja
    Lin, Honghuang
    Pool, René
    Zhu, Gu
    Macé, Aurélien
    Sidore, Carlo
    Trompet, Stella
    Mangino, Massimo
    Sabater-Lleal, Maria
    Kemp, John P
    Abbasi, Ali
    Kacprowski, Tim
    Verweij, Niek
    Smith, Albert V
    Huang, Tao
    Marzi, Carola
    Feitosa, Mary F
    Lohman, Kurt K
    Kleber, Marcus E
    Milaneschi, Yuri
    Mueller, Christian
    Huq, Mahmudul
    Vlachopoulou, Efthymia
    Lyytikäinen, Leo-Pekka
    Oldmeadow, Christopher
    Deelen, Joris
    Perola, Markus
    Zhao, Jing Hua
    Feenstra, Bjarke
    Amini, Marzyeh
    Lahti, Jari
    Schraut, Katharina E
    Fornage, Myriam
    Suktitipat, Bhoom
    Chen, Wei-Min
    Li, Xiaohui
    Nutile, Teresa
    Malerba, Giovanni
    Luan, Jian'an
    Bak, Tom
    Schork, Nicholas
    Del Greco M, Fabiola
    Thiering, Elisabeth
    Mahajan, Anubha
    Marioni, Riccardo E
    Mihailov, Evelin
    Eriksson, Joel
    Ozel, Ayse Bilge
    Zhang, Weihua
    Nethander, Maria
    Cheng, Yu-Ching
    Aslibekyan, Stella
    Ang, Wei
    Gandin, Ilaria
    Yengo, Loïc
    Portas, Laura
    Kooperberg, Charles
    Hofer, Edith
    Rajan, Kumar B
    Schurmann, Claudia
    den Hollander, Wouter
    Ahluwalia, Tarunveer S
    Zhao, Jing
    Draisma, Harmen H M
    Ford, Ian
    Timpson, Nicholas
    Teumer, Alexander
    Huang, Hongyan
    Wahl, Simone
    Liu, YongMei
    Huang, Jie
    Uh, Hae-Won
    Geller, Frank
    Joshi, Peter K
    Yanek, Lisa R
    Trabetti, Elisabetta
    Lehne, Benjamin
    Vozzi, Diego
    Verbanck, Marie
    Biino, Ginevra
    Saba, Yasaman
    Meulenbelt, Ingrid
    O'Connell, Jeff R
    Laakso, Markku
    Giulianini, Franco
    Magnusson, Patrik K E
    Ballantyne, Christie M
    Hottenga, Jouke Jan
    Montgomery, Grant W
    Rivadineira, Fernando
    Rueedi, Rico
    Steri, Maristella
    Herzig, Karl-Heinz
    Stott, David J
    Menni, Cristina
    Frånberg, Mattias
    St Pourcain, Beate
    Felix, Stephan B
    Pers, Tune H
    Bakker, Stephan J L
    Kraft, Peter
    Peters, Annette
    Vaidya, Dhananjay
    Delgado, Graciela
    Smit, Johannes H
    Großmann, Vera
    Sinisalo, Juha
    Seppälä, Ilkka
    Williams, Stephen R
    Holliday, Elizabeth G
    Moed, Matthijs
    Langenberg, Claudia
    Räikkönen, Katri
    Ding, Jingzhong
    Campbell, Harry
    Sale, Michele M
    Chen, Yii-Der I
    James, Alan L
    Ruggiero, Daniela
    Soranzo, Nicole
    Hartman, Catharina A
    Smith, Erin N
    Berenson, Gerald S
    Fuchsberger, Christian
    Hernandez, Dena
    Tiesler, Carla M T
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Liewald, David
    Fischer, Krista
    Mellström, Dan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wang, Yunmei
    Scott, William R
    Lorentzon, Matthias
    Beilby, John
    Ryan, Kathleen A
    Pennell, Craig E
    Vuckovic, Dragana
    Balkau, Beverly
    Concas, Maria Pina
    Schmidt, Reinhold
    Mendes de Leon, Carlos F
    Bottinger, Erwin P
    Kloppenburg, Margreet
    Paternoster, Lavinia
    Boehnke, Michael
    Musk, A W
    Willemsen, Gonneke
    Evans, David M
    Madden, Pamela A F
    Kähönen, Mika
    Kutalik, Zoltán
    Zoledziewska, Magdalena
    Karhunen, Ville
    Kritchevsky, Stephen B
    Sattar, Naveed
    Lachance, Genevieve
    Clarke, Robert
    Harris, Tamara B
    Raitakari, Olli T
    Attia, John R
    van Heemst, Diana
    Kajantie, Eero
    Sorice, Rossella
    Gambaro, Giovanni
    Scott, Robert A
    Hicks, Andrew A
    Ferrucci, Luigi
    Standl, Marie
    Lindgren, Cecilia M
    Starr, John M
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Li, Jun Z
    Chambers, John C
    Mori, Trevor A
    de Geus, Eco J C N
    Heath, Andrew C
    Martin, Nicholas G
    Auvinen, Juha
    Buckley, Brendan M
    de Craen, Anton J M
    Waldenberger, Melanie
    Strauch, Konstantin
    Meitinger, Thomas
    Scott, Rodney J
    McEvoy, Mark
    Beekman, Marian
    Bombieri, Cristina
    Ridker, Paul M
    Mohlke, Karen L
    Pedersen, Nancy L
    Morrison, Alanna C
    Boomsma, Dorret I
    Whitfield, John B
    Strachan, David P
    Hofman, Albert
    Vollenweider, Peter
    Cucca, Francesco
    Jarvelin, Marjo-Riitta
    Jukema, J Wouter
    Spector, Tim D
    Hamsten, Anders
    Zeller, Tanja
    Uitterlinden, André G
    Nauck, Matthias
    Gudnason, Vilmundur
    Qi, Lu
    Grallert, Harald
    Borecki, Ingrid B
    Rotter, Jerome I
    März, Winfried
    Wild, Philipp S
    Lokki, Marja-Liisa
    Boyle, Michael
    Salomaa, Veikko
    Melbye, Mads
    Eriksson, Johan G
    Wilson, James F
    Penninx, Brenda W J H
    Becker, Diane M
    Worrall, Bradford B
    Gibson, Greg
    Krauss, Ronald M
    Ciullo, Marina
    Zaza, Gianluigi
    Wareham, Nicholas J
    Oldehinkel, Albertine J
    Palmer, Lyle J
    Murray, Sarah S
    Pramstaller, Peter P
    Bandinelli, Stefania
    Heinrich, Joachim
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA.
    Deary, Ian J
    Mägi, Reedik
    Vandenput, Liesbeth
    van der Harst, Pim
    Desch, Karl C
    Kooner, Jaspal S
    Ohlsson, Claes
    Hayward, Caroline
    Lehtimäki, Terho
    Shuldiner, Alan R
    Arnett, Donna K
    Beilin, Lawrence J
    Robino, Antonietta
    Froguel, Philippe
    Pirastu, Mario
    Jess, Tine
    Koenig, Wolfgang
    Loos, Ruth J F
    Evans, Denis A
    Schmidt, Helena
    Smith, George Davey
    Slagboom, P Eline
    Eiriksdottir, Gudny
    Morris, Andrew P
    Psaty, Bruce M
    Tracy, Russell P
    Nolte, Ilja M
    Boerwinkle, Eric
    Visvikis-Siest, Sophie
    Reiner, Alex P
    Gross, Myron
    Bis, Joshua C
    Franke, Lude
    Franco, Oscar H
    Benjamin, Emelia J
    Chasman, Daniel I
    Dupuis, Josée
    Snieder, Harold
    Dehghan, Abbas
    Alizadeh, Behrooz Z
    Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders2018In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, no 5, p. 691-706, article id S0002-9297(18)30320-3Article in journal (Refereed)
    Abstract [en]

    C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

  • 20.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Population-based cardiovascular cohort studies in Uppsala2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 16-20Article in journal (Refereed)
    Abstract [en]

    The first population-based cohort study in Uppsala with the aim to study cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle-aged men has since then been followed in a longitudinal fashion for almost 50 years. This study has been followed by the PIVUS study, investigating 1000 men and women at ages 70, 75, and 80. A very detailed examination has also been performed in 500 subjects aged 50 years, the POEM study. In recent years, a high-throughput study conducted in 13000 subjects has also been performed, named EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS study. Taken together, these cardiovascular-oriented studies constitute a very rich source for cardiovascular epidemiological research in Uppsala. This review summarizes the design of these studies and highlights some of the important results published based on data from these studies.

  • 21.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Elmstahl, Solve
    Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Div Geriatr Med, Malmo, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Cardiometabolic Proteins Associated with Metabolic Syndrome2019In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518Article in journal (Refereed)
    Abstract [en]

    Background: Although metabolic syndrome (MetS) was described in the late 80s, the molecular mechanisms underlying clustering of risk factors in certain individuals are not fully understood. The present study used targeted proteomics to establish cardiometabolic proteins related to all MetS components, thereby providing new hypotheses regarding pathways involved in the pathogenesis of MetS.

    Methods: In the EpiHealth study, 249 cardiometabolic proteins were measured by proximity extension assay (PEA) and related to the five MetS components [consensus-modified National Cholesterol Education Program (NCEP) criteria] in 2,444 participants aged 45-75 years (50% women).

    Results: Thirty-one proteins were associated with systolic blood pressure following adjustment for age and sex (P < 0.000040, taking multiple testing into account). The corresponding number of proteins significantly associated with fasting glucose, waist circumference, high-density lipoprotein cholesterol, and serum triglycerides were 58, 132, 127, and 148. Twenty-two proteins were significantly related to all 5 MetS components, and of those, 20 were with MetS as a binary outcome (n = 600, 24% of the sample) following adjustment for age, sex, fat mass, and lifestyle factors (alcohol intake, smoking, education, and exercise habits).

    Conclusion: Using targeted proteomics, we identified 20 proteins reflecting a range of pathways, such as immunomodulation at different levels; regulation of adipocyte differentiation; lipid, carbohydrate, and amino acid metabolism; or insulin-like growth factor signaling, to be strongly associated with MetS independently of fat mass and lifestyle factors. Whether some of these proteins are causally involved in the pathogenesis of clustering of multiple risk factors in the same individual remains to be investigated.

  • 22.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal, Sweden.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, BioVenture Hub, Mölndal, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Proof of principle study of a detailed whole-body image analysis technique, "Imiomics", regarding adipose and lean tissue distribution2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 7388Article in journal (Refereed)
    Abstract [en]

    This "proof-of-principle" study evaluates if the recently presented "Imiomics" technique could visualize how fat and lean tissue mass are associated with local tissue volume and fat content at high/unprecedented resolution. A whole-body quantitative water-fat MRI scan was performed in 159 men and 167 women aged 50 in the population-based POEM study. Total fat and lean mass were measured by DXA. Fat content was measured by the water-fat MRI. Fat mass and distribution measures were associated to the detailed differences in tissue volume and fat concentration throughout the body using Imiomics. Fat mass was positively correlated (r > 0.50, p < 0.05) with tissue volume in all subcutaneous areas of the body, as well as volumes of the liver, intraperitoneal fat, retroperitoneal fat and perirenal fat, but negatively to lung volume. Fat mass correlated positively with volumes of paravertebral muscles, and muscles in the ventral part of the thigh and lower limb. Fat mass was distinctly correlated with the fat content in subcutaneous adipose tissue at the trunk. Lean mass was positively related to the large skeletal muscles and the skeleton. The present study indicates the Imiomics technique to be suitable for studies of fat and lean tissue distribution, and feasible for large scale studies.

  • 23.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lifetime change in central and peripheral haemodynamics in relation to exercise capacity2019In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 39, no 4, p. 261-275Article in journal (Refereed)
    Abstract [en]

    Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle-aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima-media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end-diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle-aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity.

  • 24.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease2019In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 2, p. 325-330Article in journal (Refereed)
    Abstract [en]

    Objective: Left ventricular hypertrophy (LVH) is related to a poor prognosis. We aimed to determine how left ventricular (LV) geometry changes over time, and how this relates to future cardiovascular disease.

    Methods: In the Prospective Study of the Vasculature in Uppsala Seniors study, 1016 individuals were investigated with echocardiography at age 70. This was repeated after 5 and 10 years. Incident cardiovascular disease (myocardial infarction, stroke, and heart failure, n = 163) was recorded over 10 years.

    Results: LV mass index (LVMI) and LV end-diastolic diameter (LVEDD) progressively increased over 10 years, while LV thickness declined (P< 0.0001 for all). Adjusting for traditional cardiovascular risk factors, LVMI at baseline, but not LVEDD, was significantly associated with incident cardiovascular disease [hazard ratio (HR) 1.02, 95% confidence interval 1.003-1.03, P = 0.019]. When adding the change in LVMI, or change in LVEDD, between ages 70 and 75 years to the models and using the time between 75 and 80 as follow-up (in total 82 incident cases), neither the change in LVMI nor the change in LVEDD were significant. Using updated information on LV geometric groups, an increased risk was seen for concentric LVH as compared with the normal group following adjustment for traditional risk factors (HR 2.29, P = 0.0014, 95% confidence interval 1.38-3.82). Eccentric LVH and concentric remodeling were not associated with a statistically significant increased risk of cardiovascular disease.

    Conclusion: In elderly individuals without myocardial infarction, a progressive dilatation of the LV was seen over 10 years. However, the LV dilation seen over time in this age group was not associated with a major increase in risk of future cardiovascular disease.

  • 25.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnlov, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Longitudinal effects of aging on plasma proteins levels in older adults - associations with kidney function and hemoglobin levels2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0212060Article in journal (Refereed)
    Abstract [en]

    Background A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels. Material and methods In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured. Results Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships. Conclusion The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.

  • 26.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Proteomic profiling of endothelium-dependent vasodilation2019In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 1, p. 216-222Article in journal (Refereed)
    Abstract [en]

    Objective: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intraarterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).

    Results: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate < 0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.

    Conclusion: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

  • 27.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, p. E18-E18Article in journal (Other academic)
  • 28.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thurner, Matthias
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Robertson, Neil R.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Torres, Jason M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Rayner, N. William
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Payne, Anthony J.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Steinthorsdottir, Valgerdur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Grarup, Niels
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Schmidt, Ellen M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Sarnowski, Chloe
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Magill, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Nano, Jana
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Gieger, Christian
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Trompet, Stella
    Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Below, Jennifer E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Div Genome Res, Chungcheongbuk Do, South Korea.
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Petty, Lauren E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England.
    Bennett, Amanda J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Bork-Jensen, Jette
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Med Sch, Ann Arbor, MI 48109 USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Kardt, Kai-Uwe Ec
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany;Charite Univ Med Berlin, German Chron Kidney Dis Study, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Math & Stat, Tartu, Estonia.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Locke, Adam E.
    Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA;Washington Univ, Sch Med, Dept Med, Div Genom & Bioinformat, St Louis, MO 63110 USA.
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Ntalla, Loanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
    Nylander, Vibe
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Schoenherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Florez, Jose C.
    Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Diabet Res Ctr, Dept Med, Diabet Unit, Boston, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    France, Oscar H.
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, Leibniz Ctr Diabet Res, Dusseldorf, Germany.
    Ikram, M. Arfan
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Ligthart, Symen
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Frederiksberg, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Lyssenko, Valeriya
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Kuwait, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA;NHLBI, Framingham Heart Stud, Framingham, MA USA.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Collins, Francis S.
    NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Grallert, Harald
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Helmholtz Zentrum Munchen, Clin Cooparat Grp Type Diabet 2, Munich, Germany;Tech Univ, Helmholtz Zentrum Munchen, Clin Cooparat Grp, Nutrigen & Type Diabet 2, Munich, Germany.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Dehghan, Abbas
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Koettgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
    Rotter, Jerome, I
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Med, LABioMed, Torrance, CA 90509 USA.
    Marchini, Jonathan
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Pedersen, Oluf
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gloyn, Anna L.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Morris, Andrew P.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    McCarthy, Mark, I
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 11, p. 1505-+Article in journal (Refereed)
    Abstract [en]

    We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

  • 29.
    Marklund, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Lindgren, Cecilia M.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England;Univ Oxford, Big Data Inst, Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7LF, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 11, article id 1791Article in journal (Refereed)
    Abstract [en]

    Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of delta-5-desaturase (D5D), delta-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 x 10(-70)) and adipose tissue (p = 1.1 x 10(-27)). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 x 10(-67); PDXDCI, p = 4.8 x 10(-8); and near MC4R, p = 3.7 x 10(-8)) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 x 10(-19)). Genetic variants near MC4R were associated with IS (p = 3.8 x 10(-3)). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.

  • 30.
    Marklund, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Wu, Jason H. Y.
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia.
    Imamura, Fumiaki
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Del Gobbo, Liana C.
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Fretts, Amanda
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    de Goede, Janette
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Shi, Peilin
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Tintle, Nathan
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Wennberg, Maria
    Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
    Chen, Tzu-An
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Otto, Marcia C. de Oliveira
    Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
    Hirakawa, Yoichiro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Fukuoka, Japan.
    Eriksen, Helle Hojmark
    Aalborg Univ Hosp, Unit Epidemiol & Biostat, Aalborg, Denmark.
    Kroeger, Janine
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Laguzzi, Federica
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lankinen, Maria
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Murphy, Rachel A.
    Univ British Columbia, Vancouver, BC, Canada.
    Prem, Kiesha
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Samieri, Cecilia
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Virtanen, Jyrki
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Wood, Alexis C.
    Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Houston, TX 77030 USA.
    Wong, Kerry
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Yang, Wei-Sin
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan.
    Zhou, Xia
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Baylin, Ana
    Univ Michigan, Sch Publ Hlth, Dept Nutr Sci, Ann Arbor, MI 48109 USA;Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Boer, Jolanda M. A.
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands.
    Brouwer, Ingeborg A.
    Vrije Univ, Hlth Sci, Amsterdam, Netherlands.
    Campos, Hannia
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Chaves, Paulo H. M.
    Florida Int Univ, Herbert Wertheim Coll Med, Benjamin Leon Geriatr Res & Educ, Miami, FL 33199 USA.
    Chien, Kuo-Liong
    Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan;Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    de Faire, Ulf
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Djousse, Luc
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland.
    El-Abbadi, Naglaa
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Forouhi, Nita G.
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Gaziano, J. Michael
    Brigham & Womens Hosp, Boston Vet Affairs Healthcare Syst, Boston, MA 02115 USA.
    Geleijnse, Johanna M.
    Wageningen Univ, Div Human Nutr, Wageningen, Netherlands.
    Gigante, Bruna
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Giles, Graham
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Guallar, Eliseo
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Div Environm Epidemiol, Baltimore, MD USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.
    Harris, Tamara
    NIA, Bethesda, MD 20892 USA.
    Harris, William S.
    Univ South Dakota, Dept Internal Med, Sanford Sch Med, Sioux Falls, SD USA;OmegaQuant Analyt LLC, Sioux Falls, SD USA.
    Helmer, Catherine
    Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, TUMR 1219, Bordeaux, France.
    Hellenius, Mai-Lis
    Karolinska Univ Hosp, Karolinska Inst, Cardiol Unit, Dept Med, Stockholm, Sweden.
    Hodge, Allison
    Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Jacques, Paul F.
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA;USDA, Jean Mayer Human Nutr Res Ctr, Boston, MA USA.
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit Skelleftea, Umea, Sweden.
    Kalsbeek, Anya
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Koh, Woon-Puay
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.
    Leander, Karin
    Karolinska Inst, Unit Cardiovasc Epidemiol, Inst Environm Med, Stockholm, Sweden.
    Lin, Hung-Ju
    Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Luben, Robert
    Univ Cambridge, Dept Publ Hlth & Primary Care, Sch Clin Med, Cambridge, England.
    Luo, Juhua
    Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN USA.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98195 USA.
    Mursu, Jaakko
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Fukuoka, Japan.
    Overvad, Kim
    Aarhus Univ, Dept Publ Hlth, Sect Epidemiol, Aarhus, Denmark;Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Study, Seattle, WA USA;Univ Washington, Dept Epidemiol, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Study, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rimm, Eric
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
    Siscovick, David
    New York Acad Med, New York, NY USA.
    Nielsen, Michael Skjelbo
    Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
    Smith, Albert, V
    Iceland Heart Assoc, Kopavogur, Iceland.
    Steffen, Brian T.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Steffen, Lyn
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Sun, Qi
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Tsai, Michael Y.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
    Tunstall-Pedoe, Hugh
    Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland.
    Uusitupa, Matti I. J.
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
    van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Veenstra, Jenna
    Dordt Coll, Dept Math & Stat, Sioux Ctr, IA USA.
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, Bilthoven, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Wareham, Nick
    Univ Cambridge, MRC, Epidemiol Unit, Cambridge, England.
    Willett, Walter
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Dept Med, Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Woodward, Mark
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia;Univ New South Wales, Fac Med, Sydney, NSW, Australia;Univ Dundee, Cardiovasc Epidemiol Unit, Inst Cardiovasc Res, Dundee, Scotland;Univ Oxford, George Inst Global Hlth, Oxford, England.
    Yuan, Jian-Min
    Univ Pittsburgh, Div Canc Control & Populat Sci, UPMC Hillman Canc, Pittsburgh, PA 15260 USA;Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Lemaitre, Rozenn N.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Mozaffarian, Dariush
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 21, p. 2422-2436Article in journal (Refereed)
    Abstract [en]

    Background:

    Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.

    Methods:

    We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).

    Results:

    In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.

    Conclusions:

    In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

  • 31.
    Mohammadi, H.
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Ohm, J.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Discacciati, A.
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Hambraeus, K.
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden.
    Jernberg, T.
    Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Svensson, P.
    Karolinska Inst, Dept Med, Stockholm, Sweden.
    Abdominal obesity associates to incident atherosclerotic cardiovascular disease after myocardial infarction2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no Suppl. 1, p. 237-238, article id P1121Article in journal (Other academic)
  • 32. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 33.
    Mubanga, Mwenya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, article id e023447Article in journal (Refereed)
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

  • 34.
    Oscarsson, Jan
    et al.
    AstraZeneca Gothenburg, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Onnerhag, Kristina
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sunden, Mattias
    AstraZeneca Gothenburg, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Johansson, Lars
    Antaros Med AB, Molndal, Sweden.
    Jansson, Per-Anders
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden.
    Moris, Linda
    Karolinska Univ Hosp, Karolinska Trial Alliance, Solna, Sweden.
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Effects of free omega-3 carboxylic acids and fenofibrate on liver fat content in patients with hypertriglyceridemia and non-alcoholic fatty liver disease: A double-blind, randomized, placebo-controlled study2018In: Journal of Clinical Lipidology, ISSN 1933-2874, E-ISSN 1876-4789, Vol. 12, no 6, p. 1390-1403Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment with omega-3 fatty acids and fenofibrates reduces serum triglyceride levels, but few studies have compared the effect of these agents on liver fat. OBJECTIVE: The aim of the EFFECT I trial (NCT02354976) was to determine the effects of free omega-3 carboxylic acids (OM-3CA) and fenofibrate on liver fat in overweight or obese individuals with non-alcoholic fatty liver disease and hypertriglyceridemia. METHODS: Seventy-eight patients were randomized to receive oral doses of 4 g OM-3CA (n = 25), 200 mg fenofibrate (n = 27), or placebo (n = 26) for 12 weeks in a double-blind, parallel-group study. Liver proton density fat fraction (PDFF) and volume, pancreas volume, and adipose tissue volumes were assessed by magnetic resonance imaging. RESULTS: Changes in liver PDFF at 12 weeks were not significantly different across treatment groups (relative changes from baseline: placebo, +4%; OM-3CA, -2%; and fenofibrate, +17%). The common PNPLA3 genetic polymorphism (I148M) did not significantly influence the effects of OM-3CA or fenofibrate on liver PDFF. Fenofibrate treatment significantly increased liver and pancreas volumes vs placebo treatment, and the changes in liver and pancreas volumes were positively correlated (rho 0.45, P = .02). Total liver fat volume increased significantly in patients using fenofibrate vs OM-3CA (+23% vs 3%, P = .04). Compared with OM-3CA, fenofibrate increased total liver fat and liver volume. Serum triglycerides decreased with OM-3CA (-26%, P = .02) and fenofibrate (-38%, P < .001) vs placebo. In contrast to OM-3CA, fenofibrate reduced plasma docosahexaenoic acid levels and increased plasma acetylcarnitine and butyrylcarnitine levels, estimated delta-9 desaturase activity and the concentration of urine F2-isoprostanes. CONCLUSIONS: OM-3CA and fenofibrate reduced serum triglycerides but did not reduce liver fat. Fenofibrate increased total liver volume and total liver fat volume vs OM-3CA, indicating a complex effect of fenofibrate on human hepatic lipid metabolism.

  • 35.
    Pennells, Lisa
    et al.
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Kaptoge, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Wood, Angela
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Sweeting, Mike
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Zhao, Xiaohui
    Univ Cambridge, Dept Physiol Dev & Neurosci, Downing St, Cambridge CB2 3EG, England.
    White, Ian
    UCL, MRC Clin Trials Unit, 90 High Holborn, London WC1V 6LJ, England.
    Burgess, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;Univ Cambridge, Cambridge Inst Publ Hlth, MRC Biostat Unit, Forvie Site,Robinson Way, Cambridge CB2 0SR, England.
    Willeit, Peter
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;Med Univ Innsbruck, Dept Neurol & Neurosurg, Anichstra 35, A-6020 Innsbruck, Austria.
    Bolton, Thomas
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Moons, Karel G. M.
    Univ Med Ctr Utrecht, Julius Ctr, Res Program Methodol, Epidemiol Methodol, Heidelberglaan 100, NL-3584 Utrecht, Netherlands.
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr, Res Program Cardiovasc Epidemiol, Dept Epidemiol, Heidelberglaan 100, NL-3584 Utrecht, Netherlands;ProspectEPIC, Utrecht, Netherlands.
    Selmer, Randi
    Norwegian Inst Publ Hlth, Div Epidemiol, Postboks 222 Skoyen, N-0213 Oslo, Norway.
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England;EPICNOR, London, England;RANCHO, Utrecht, Netherlands.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Hjartavernd Holtasmari 1, IS-201 Kopavogur, Iceland;Univ Iceland, Fac Med, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland.
    Assmann, Gerd
    Assmann Fdn Prevent, Gronowskistr 33, D-48161 Munster, Germany;PROCAM, Newton, MA USA.
    Amouyel, Philippe
    Inst Pasteur, 1 Rue Professeur Calmette, F-59019 Lille, France;PRIME, Newton, MA USA.
    Salomaa, Veikko
    Nat Inst Hlth & Welf, Mannerheimintie 166, Helsinki 00271, Finland;KAREL72, Isa Town, Bahrain.
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, 1-19 Torrington Pl, London WC1E 7HB, England;WHITE I, Viana Do Castelo, Portugal.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Dept Clin Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
    Blaha, Michael J.
    Johns Hopkins Univ Hosp, Ciccarone Ctr Prevent Heart Dis, 1800 Orleans St, Baltimore, MD 21287 USA.
    Kuller, Lewis H.
    Univ Pittsburgh, Dept Epidemiol, 200 Lothrop St, Pittsburgh, PA 15212 USA;MRFIT, Utrecht, Netherlands.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Neuenheimer Feld 581, D-69120 Heidelberg, Germany;Heidelberg Univ, Grabengasse 1, D-69117 Heidelberg, Germany;WCWC, Viana Do Castelo, Portugal.
    Gillum, Richard F.
    Howard Univ, Coll Med, Dept Med, 2041 Georgia Ave, Washington, DC 20060 USA;NHANES III, Utrecht, Netherlands.
    Meisinger, Christa
    German Res Ctr Environm Hlth, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;MONICA KORA2, Karachi, Pakistan;MONICA KORA3, Karachi, Pakistan.
    Ford, Ian
    Univ Glasgow, Inst Hlth & Wellbeing, Boyd Orr Bldg,Univ Ave, Glasgow G12 8QQ, Lanark, Scotland;WOSCOPS, Viana Do Castelo, Portugal.
    Knuiman, Matthew W.
    Univ Western Australia, Sch Populat & Global Hlth, Fac Hlth & Med Sci, 35 Stirling Highway, Perth, WA 6009, Australia;BHS, London, England.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Acad, Medicinaregatan 3, S-41390 Gothenburg, Sweden;Sahlgrens Univ Hosp, Wallenberg Lab, Bla Stradket 5, S-41345 Gothenburg, Sweden;GOT043, Belfast, Antrim, North Ireland;MOSWEGOT, Utrecht, Netherlands.
    Lawlor, Debbie A.
    Univ Bristol, Dept Social Med, Bristol BS8 2PR, Avon, England.
    Volzke, Henry
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Ellernholzstr 1-2, D-17489 Greifswald, Germany.
    Cooper, Cyrus
    Univ Southampton, MRC Lifecourse Epidemiol Unit, Tremona Rd, Southampton SO16 6YD, Hants, England.
    Ibanez, Alejandro Marin
    San Jose Norte Hlth Ctr, 16 Lugar Santuario Cabanas, Zaragoza 50013, Spain.
    Casiglia, Edoardo
    Univ Padua, Dept Med, 2 Via Giustiniani, I-35128 Padua, Italy;CASTEL, New York, NY USA.
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, 1 Yliopistonranta, Kuopio, Finland.
    Cooper, Jackie A.
    UCL, Ctr Cardiovasc Genet, 5 Univ St, London WC1E 6JF, England;NPHSII, Utrecht, Netherlands.
    Rodriguez, Beatriz
    Univ Hawaii, Dept Geriatr Med, 1960 East West Rd, Honolulu, HI 96822 USA;HONOL, Tokyo, Japan.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Barrett-Connor, Elizabeth
    Univ Calif San Diego, 9500 Gilman Dr, La Jolla, CA 92093 USA.
    Dankner, Rachel
    Gertner Inst Epidemiol & Hlth Policy Res, Sheba Med Ctr, Unit Cardiovasc Epidemiol, IL-52621 Tel Hashomer, Israel;Tel Aviv Univ, Sch Publ Hlth, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel.
    Nietert, Paul J.
    Med Univ South Carolina, Dept Publ Hlth Sci, 135 Cannon St, Charleston, SC 29425 USA;CHARL, Greenville, SC USA.
    Davidson, Karina W.
    Columbia Univ Irving Med Ctr, Dept Med, 622 West 168th St, New York, NY 10032 USA.
    Wallace, Robert B.
    Univ Iowa, Coll Publ Hlth, 145 N Riverside Dr, Iowa City, IA 52242 USA.
    Blazer, Dan G.
    Duke Univ, Med Ctr, Dept Surg, 2301 Erwin Rd, Durham, NC 27707 USA.
    Bjorkelund, Cecilia
    Univ Gothenburg, Dept Publ Hlth & Community Med, Medicinaregatan 16, S-41390 Gothenburg, Sweden;GOTOW, Belfast, Antrim, North Ireland.
    Donfrancesco, Chiara
    ISS, Dysmetabol & Aging Associated Dis, Dept Cardiovasc, 299 Viale Regina Elena, I-00161 Rome, Italy;FINE IT, Heidelberg, Germany.
    Krumholz, Harlan M.
    Yale Sch Med, 1 Church St, New Haven, CT 06510 USA.
    Nissinen, Aulikki
    Nat Inst Hlth & Welf, Mannerheimintie 166, Helsinki 00271, Finland;FINE FIN, Heidelberg, Germany.
    Davis, Barry R.
    Univ Texas Houston, Sch Publ Hlth, Dept Biostat, 1200 Pressler St, Houston, TX 77030 USA.
    Coady, Sean
    NHLBI, Div Cardiovasc Sci, 31 Ctr Dr, Bethesda, MD 20892 USA.
    Whincup, Peter H.
    St Georges Univ London, Populat Hlth Res Inst, Cranmer Terrace, London SW17 0RE, England;BRHS, Bridgewater, MA USA.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, 5 Oster Farimagsgade, DK-1014 Copenhagen, Denmark;Univ Copenhagen, Dept Publ Hlth, 5 Oster Farimagsgade, DK-1014 Copenhagen, Denmark;Aalborg Univ, Fredrik Bajers Vej 5, DK-9100 Aalborg, Denmark.
    Ducimetiere, Pierre
    Univ Paris 05, Fac Med, 12 Rue Ecole Med, F-75006 Paris, France.
    Trevisan, Maurizio
    CUNY, Sch Med, City Coll New York, 160 Convent Ave, New York, NY 10031 USA;RIFLE, Utrecht, Netherlands.
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden.
    Crespo, Carlos J.
    Portland State Univ, Sch Community Hlth, 506 SW Mill St, Portland, OR 97201 USA;PRHHP, Newton, MA USA.
    Meade, Tomw.
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, Keppel St, London WC1E 7HT, England.
    Visser, Marjolein
    Vrije Univ Amsterdam, VU Univ, Med Ctr, Dept Hlth Sci, De Boelelaan 1085, NL-1081 Amsterdam, Netherlands;LASA, Karachi, Pakistan.
    Kromhout, Daan
    Univ Grogingen, Univ Med Ctr Groningen, Dept Epidemiol, Hanzepl 1, NL-9713 Groningen, Netherlands.
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol & Neurosurg, Anichstra 35, A-6020 Innsbruck, Austria.
    Daimon, Makoto
    Yamagata Univ, Fac Med, 1-4-12 Kojirakawa Machi, Yamagata 9908560, Japan.
    Price, Jackie F.
    Univ Edinburgh, Old Med Sch, Usher Inst Populat Hlth Sci & Informat, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
    de la Camara, Agustin Gomez
    Hosp 12 Octubre, Dept Clin Res, Av Cordoba, E-28041 Madrid, Spain;DRECE, Madrid, Spain.
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Albinusdreef 2, NL-2333 Leiden, Netherlands.
    Lamarche, Benoit
    Univ Laval, Pavillon Ferdinand Vandry,2440 Hochelaga, Quebec City, PQ G1V 0A6, Canada.
    Onat, Altan
    Istanbul Univ, Cerrahpasa Fac Med, Dept Cardiol, TR-34452 Istanbul, Turkey.
    Simons, Leon A.
    UNSW, Fac Med, Sydney, NSW 2052, Australia.
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Doctor Molewaterpl 40, NL-3015 Rotterdam, Netherlands.
    Ben-Shlomo, Yoav
    Univ Bristol, Bristol Neurosci, Queens Rd, Bristol BS8 1QU, Avon, England;CAPS, Oxford, England.
    Gallacher, John
    Univ Oxford, Warneford Hosp, Dept Psychiat, Warneford Lane, Oxford OX3 7JX, England;CAPS, Oxford, England.
    Dekker, Jacqueline M.
    Vrije Univ Amsterdam, Med Ctr, Inst Hlth & Care Res, De Boelelaan 1085, NL-1081 Amsterdam, Netherlands.
    Arima, Hisatomi
    Kyushu Univ, Nishi Ku, 744 Motooka, Fukuoka, Fukuoka 8190395, Japan.
    Shara, Nawar
    MedStar Hlth Res Inst, Dept Biostat & Bioinformat, 6525 Belcrest Rd, Hyattsville, MD 20782 USA.
    Tipping, RobertW.
    Merck, Clin Biostat, 2000 Galloping Hill Rd, Kenilworth, NJ 07033 USA.
    Roussel, Ronan
    INSERM, Ctr Rech Cordeliers, 15 Rue Ecole Med, F-57006 Paris, France.
    Brunner, Eric J.
    UCL, Inst Epidemiol & Hlth, 1-19 Torrington Pl, London WC1E 7HB, England;WHITE II, Viana Do Castelo, Portugal.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsches Herzzentrum Munchen, 21 Arcisstr, D-80333 Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Biedersteiner Str 29, D-80802 Munich, Germany;MONICA KORA2, Karachi, Pakistan;MONICA KORA3, Karachi, Pakistan.
    Sakurai, Masaru
    Kanazawa Med Univ, Dept Social & Environm Med, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan.
    Pavlovic, Jelena
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Doctor Molewaterpl 40, NL-3015 Rotterdam, Netherlands.
    Gansevoort, Ron T.
    Univ Grogingen, Univ Med Ctr Groningen, Dept Internal Med, Hanzeplein 1, NL-9713 Groningen, Netherlands.
    Nagel, Dorothea
    Univ Munich, Klinikum Univ Munchen, 15 Marchioninistr, D-81377 Munich, Germany;GRIPS, Tokyo, Japan.
    Goldbourt, Uri
    Tel Aviv Univ, Sch Publ Hlth, Sackler Fac Med, Dept Epidemiol & Prevent Med, IL-69978 Tel Aviv, Israel.
    Barr, Elizabeth L. M.
    Baker Heart & Diabet Inst, Clin Diabet & Epidemiol, 75 Commercial Rd, Melbourne, Vic 3004, Australia.
    Palmieri, Luigi
    ISS, Dysmetabol & Aging Associated Dis, Dept Cardiovasc, 299 Viale Regina Elena, I-00161 Rome, Italy;CUORE, Madrid, Spain.
    Njolstad, Inger
    Univ Tromso, Dept Publ Hlth, Hansine Hansens Veg 18, Tromso, Norway.
    Sato, Shinichi
    Chiba Prefectural Inst Publ Hlth, Chuo Ku, 666-2 Nito No Machi, Chiba 2608715, Japan;IKNS, Isa Town, Bahrain.
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Antonie Leeuwenhoeklaan 9, NL-3721 Bilthoven, Netherlands;MCVDRFP, Karachi, Pakistan;MORGEN, Utrecht, Netherlands.
    Varghese, Cherian V.
    WHO, Noncommunicable Dis Disabil Violence & Injury Pre, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
    Graham, Ian
    Univ Dublin, Coll Green, Trinity Coll Dublin, Sch Med, Dublin 2, Ireland.
    Onuma, Oyere
    WHO, Noncommunicable Dis Disabil Violence & Injury Pre, 20 Ave Appia, CH-1211 Geneva 27, Switzerland.
    Greenland, Philip
    Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 420 East Super St, Chicago, IL 60611 USA.
    Woodward, Mark
    Univ Oxford, George Inst Global Hlth, 75 George St, Oxford OX1 2BQ, England;Univ New South Wales, George Inst Global Hlth, 1 King St Newtown, Sydney, NSW 2042, Australia.
    Ezzati, Majid
    Imperial Coll London, Sch Publ Hlth, Fac Med, Norfolk Pl,St Marys Campus, London W2 1PG, England.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, 1730 Minor Ave, Seattle, WA 98101 USA;CHS, Inver Grove Hts, MN USA.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, 126 Univ Pl, Glasgow G12 8TA, Lanark, Scotland;MIDFAM, Karachi, Pakistan;WOSCOPS, Viana Do Castelo, Portugal.
    Jackson, Rod
    Univ Auckland, Fac Med & Hlth Sci, 261 Morrin Rd, Auckland, New Zealand.
    Ridker, Paul M.
    Harvard Med Sch, Brigham & Womens Hosp, 900 Commonwealth Ave, Boston, MA 02215 USA;USPHS2, Viana Do Castelo, Portugal;WHS, Viana Do Castelo, Portugal.
    Cook, Nancy R.
    Harvard Med Sch, Brigham & Womens Hosp, 900 Commonwealth Ave, Boston, MA 02215 USA.
    D'Agostino, Ralph B., Sr.
    Boston Univ, Math & Stat Dept, 111 Cummington Mall, Boston, MA 02215 USA;FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Thompson, Simon G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, 2 Worts Causeway, Cambridge CB1 8RN, England.
    Tipping, Robert W.
    AFTCAPS, Benn, Germany.
    Simpson, Lara M.
    ALLHAT, Bethesda, MD USA.
    Pressel, Sara L.
    ALLHAT, Bethesda, MD USA.
    Couper, David J.
    ARIC, Chapel Hill, NC USA.
    Nambi, Vijay
    ARIC, Chapel Hill, NC USA.
    Matsushita, Kunihiro
    ARIC, Chapel Hill, NC USA.
    Folsom, Aaron R.
    ARIC, Chapel Hill, NC USA.
    Shaw, Jonathan E.
    AUSDIAB, Melbourne, Vic, Australia.
    Magliano, Dianna J.
    AUSDIAB, Melbourne, Vic, Australia.
    Zimmet, Paul Z.
    AUSDIAB, Melbourne, Vic, Australia.
    Wannamethee, S. Goya
    BRHS, Bridgewater, MA USA.
    Willeit, Johann
    BRUN, Bridgewater, MA USA.
    Santer, Peter
    BRUN, Bridgewater, MA USA.
    Egger, Georg
    BRUN, Bridgewater, MA USA.
    Casas, Juan Pablo
    BWHHS, London, England.
    Amuzu, Antointtte
    BWHHS, London, England.
    Tikhonoff, Valerie
    CASTEL, New York, NY USA.
    Sutherland, Susan E.
    CHARL, Greenville, SC USA.
    Cushman, Mary
    CHS, Inver Grove Hts, MN USA.
    Sogaard, Anne Johanne
    CONOR, Tromso, Norway.
    Haheim, Lise Lund
    CONOR, Tromso, Norway.
    Ariansen, Inger
    CONOR, Tromso, Norway.
    Tybjaerg-Hansen, Anne
    COPEN, Copenhagen, Denmark.
    Jensen, Gorm B.
    COPEN, Copenhagen, Denmark.
    Schnohr, Peter
    COPEN, Copenhagen, Denmark.
    Giampaoli, Simona
    CUORE, Madrid, Spain;FINE IT, Heidelberg, Germany.
    Vanuzzo, Diego
    CUORE, Madrid, Spain.
    Panico, Salvatore
    CUORE, Madrid, Spain.
    Balkau, Beverley
    DESIR, Madrid, Spain.
    Bonnet, Fabrice
    DESIR, Madrid, Spain.
    Marre, Michel
    DESIR, Madrid, Spain.
    Herrera, Miguel Angel Rubio
    DRECE, Madrid, Spain.
    Friedlander, Yechiel
    McCallum, John
    McLachlan, Stela
    EAS, Gothenburg, Sweden.
    Guralnik, Jack
    EPESEBOS, London, England;EPESEIOW, Baltimore, MD USA;EPESENCA, Oxford, England;EPESENHA, New York, NY USA.
    Phillips, Caroline L.
    EPESEBOS, London, England.
    Wareham, Nick
    EPICNOR, London, England.
    Schottker, Ben
    ESTHER, Heidelberg, Germany.
    Saum, Kai-Uwe
    ESTHER, Heidelberg, Germany.
    Holleczek, Bernd
    ESTHER, Heidelberg, Germany.
    Tolonen, Hanna
    FINE FIN, Heidelberg, Germany.
    Jousilahti, Pekka
    FINRISK 92 97, Heidelberg, Germany.
    Harald, Kennet
    FINRISK 92 97, Heidelberg, Germany.
    Massaro, Joseph M.
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Pencina, Michael
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Vasan, Ramachandran
    FRAM, Boston, MA USA;FRAMOFF, Boston, MA USA.
    Kayama, Takamasa
    Kato, Takeo
    Oizumi, Toshihide
    Jespersen, Jorgen
    Moller, Lars
    Bladbjerg, Else Marie
    Chetrit, A.
    GOH, Belfast, Antrim, North Ireland.
    Wilhelmsen, Lars
    GOT043, Belfast, Antrim, North Ireland.
    Lissner, Lauren
    GOTOW, Belfast, Antrim, North Ireland.
    Dennison, Elaine
    HCS, Tokyo, Japan.
    Kiyohara, Yutaka
    Ninomiya, Toshiharu
    Doi, Yasufumi
    Nijpels, Giel
    Stehouwer, Coen D. A.
    Kazumasa, Yamagishi
    IKNS, Isa Town, Bahrain.
    Iso, Hiroyasu
    IKNS, Isa Town, Bahrain.
    Vartiainen, Erkki
    FINRISK 92 97, Heidelberg, Germany;KAREL72, Isa Town, Bahrain.
    Kurl, Sudhir
    KIHD, Karachi, Pakistan.
    Tuomainen, Tomi-Pekka
    KIHD, Karachi, Pakistan.
    Salonen, Jukka T.
    KIHD, Karachi, Pakistan.
    Deeg, Dorly J. H.
    LASA, Karachi, Pakistan.
    Nilsson, Peter M.
    Hedblad, Bo
    Melander, Olle
    De Boer, Ian H.
    DeFilippis, Andrew Paul
    Watt, Graham
    MIDFAM, Karachi, Pakistan.
    Verschuren, Monique
    Tverdal, Aage
    NCS, Utrecht, Netherlands.
    Kirkland, Susan
    NSHS, Newton, MA USA.
    Shimbo, Daichi
    NSHS, Newton, MA USA.
    Shaffer, Jonathan
    NSHS, Newton, MA USA.
    Bakker, Stephan J. L.
    PREVEND, Newton, MA USA.
    van der Harst, Pim
    PREVEND, Newton, MA USA.
    Hillege, Hans L.
    PREVEND, Newton, MA USA.
    Dallongeville, Jean
    PRIME, Newton, MA USA.
    Schulte, Helmut
    PROCAM, Newton, MA USA.
    Trompet, Stella
    PROSPER, Newton, MA USA.
    Smit, Roelof A. J.
    PROSPER, Newton, MA USA.
    Stott, David J.
    PROSPER, Newton, MA USA.
    Despres, Jean-Pierre
    Cantin, Bernard
    Dagenais, Gilles R.
    Laughlin, Gail
    RANCHO, Utrecht, Netherlands.
    Wingard, Deborah
    RANCHO, Utrecht, Netherlands.
    Aspelund, Thor
    REYK, Reykjavik, Iceland.
    Eiriksdottir, Gudny
    REYK, Reykjavik, Iceland.
    Gudmundsson, Elias Freyr
    Ikram, Arfan
    van Rooij, Frank J. A.
    Franco, Oscar H.
    Rueda-Ochoa, Oscar L.
    Muka, Taulant
    Glisic, Marija
    Tunstall-Pedoe, Hugh
    Howard, Barbara V.
    Zhang, Ying
    Jolly, Stacey
    Davey-Smith, George
    Can, Gunay
    Yuksel, Husniye
    Nakagawa, Hideaki
    Morikawa, Yuko
    Miura, Katsuyuki
    Ingelsson, Martin
    ULSAM, Viana Do Castelo, Portugal.
    Giedraitis, Vilmantas
    ULSAM, Viana Do Castelo, Portugal.
    Gaziano, J. Michael
    USPHS2, Viana Do Castelo, Portugal.
    Shipley, Martin
    WHITE I, Viana Do Castelo, Portugal;WHITE II, Viana Do Castelo, Portugal.
    Arndt, Volker
    WCWC, Viana Do Castelo, Portugal.
    Cook, Nancy
    WHS, Viana Do Castelo, Portugal.
    Geleijnse, Johanna M.
    ZUTE, Viana Do Castelo, Portugal.
    Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 7, p. 621-+Article in journal (Refereed)
    Abstract [en]

    Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.

    Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.

    Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

  • 36. Pulit, Sara L.
    et al.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sheth, Kevin
    Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes2018In: NEUROLOGY-GENETICS, ISSN 2376-7839, Vol. 4, no 6, article id e293Article in journal (Refereed)
    Abstract [en]

    Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. Results We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Conclusions Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

  • 37.
    Rydell, Andreas
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lisspers, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Ställberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Nowak, Christoph
    Karolinska Inst, Stockholm, Sweden.
    Carlsson, Axel
    Karolinska Inst, Stockholm, Sweden.
    Feldreich, Tobias
    Dalarna Univ, Falun, Sweden.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ärnlöv, Johan
    Karolinska Inst, Stockholm, Sweden.
    Endothelial dysfunction is associated with impaired lung function in two independent community cohorts2018In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 52Article in journal (Other academic)
  • 38.
    Sakornsakolpat, Phuwanat
    et al.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Mahidol Univ, Dept Med, Fac Med, Siriraj Hosp, Bangkok, Thailand.
    Prokopenko, Dmitry
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02114 USA.
    Lamontagne, Maxime
    Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Reeve, Nicola F.
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England.
    Guyatt, Anna L.
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England.
    Jackson, Victoria E.
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England.
    Shrine, Nick
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England.
    Qiao, Dandi
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA;Univ Washington, Dept Med, Seattle, WA 98195 USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Kim, Deog Kyeom
    Seoul Natl Univ, Coll Med, SMG SNU Boramae Med Ctr, Seoul, South Korea.
    Lee, Mi Kyeong
    NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA.
    Latourelle, Jeanne C.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
    Li, Xingnan
    Univ Arizona, Dept Med, Tucson, AZ USA.
    Morrow, Jarrett D.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Obeidat, Ma'en
    Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC, Canada.
    Wyss, Annah B.
    NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA.
    Bakke, Per
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Barr, R. Graham
    Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY USA;Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
    Beaty, Terri H.
    Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
    Belinsky, Steven A.
    Lovelace Resp Res Inst, Albuquerque, NM USA.
    Brusselle, Guy G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium;Erasmus MC, Dept Resp Med, Rotterdam, Netherlands.
    Crapo, James D.
    Natl Jewish Hlth, Div Pulm & Crit Care Med, Dept Med, Denver, CO USA.
    de Jong, Kim
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands.
    DeMeo, Dawn L.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Fingerlin, Tasha E.
    Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA;Univ Colorado Denver, Dept Biostat & Informat, Aurora, CO USA.
    Gharib, Sina A.
    Univ Washington, Computat Med Core, Ctr Lung Biol, UW Med Sleep Ctr,Dept Med, Seattle, WA 98195 USA.
    Gulsvik, Amund
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Hall, Ian P.
    Univ Nottingham, Div Resp Med, Queens Med Ctr, Nottingham, England;Nottingham Biomed Res Ctr, Natl Inst Hlth Res, Nottingham, England.
    Hokanson, John E.
    Univ Colorado, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA.
    Kim, Woo Jin
    Kangwon Natl Univ, Dept Internal Med, Sch Med, Chunchon, South Korea;Kangwon Natl Univ, Environm Hlth Ctr, Chunchon, South Korea.
    Lomas, David A.
    UCL, UCL Resp, London, England.
    London, Stephanie J.
    NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Raleigh, NC USA.
    Meyers, Deborah A.
    Univ Arizona, Dept Med, Tucson, AZ USA.
    O'Connor, George T.
    Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA;Boston Univ, Sch Med, Dept Med, Pulm Ctr, Boston, MA 02118 USA.
    Rennard, Stephen, I
    Univ Nebraska Med Ctr, Pulm Crit Care Sleep & Allergy Div, Omaha, NE USA;AstraZeneca, Clin Discovery Unit, Cambridge, England.
    Schwartz, David A.
    Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO USA;Univ Colorado Denver, Sch Med, Dept Immunol, Aurora, CO USA.
    Sliwinski, Pawel
    Inst TB & Lung Dis, Dept Resp Med 2, Warsaw, Poland.
    Sparrow, David
    Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England.
    Tal-Singer, Ruth
    GlaxoSmithKline R&D, Collegeville, PA USA.
    Tesfaigzi, Yohannes
    Lovelace Resp Res Inst, Albuquerque, NM USA.
    Vestbo, Jorgen
    Univ Manchester, Sch Biol Sci, Manchester, Lancs, England.
    Vonk, Judith M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands.
    Yim, Jae-Joon
    Seoul Natl Univ, Coll Med, Div Pulm & Crit Care Med, Dept Internal Med, Seoul, South Korea.
    Zhou, Xiaobo
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Bosse, Yohan
    Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada;Laval Univ, Dept Mol Med, Quebec City, PQ, Canada.
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA;Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
    Lahousse, Lies
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Ghent, Dept Bioanal, Ghent, Belgium.
    Silverman, Edwin K.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Boezen, H. Marike
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands.
    Wain, Louise, V
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, Natl Inst Hlth Res, Leicester Resp Biomed Res Ctr, Leicester, Leics, England.
    Tobin, Martin D.
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, Natl Inst Hlth Res, Leicester Resp Biomed Res Ctr, Leicester, Leics, England.
    Hobbs, Brian D.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Cho, Michael H.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Batini, Chiara
    Univ Leicester, Genet Epidemiol Grp, Dept Hlth Sci, Leicester, Leics, England.
    Zhao, Jing Hua
    Univ Cambridge, Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.
    Wielscher, Matthias
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England.
    Weiss, Stefan
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
    Kentistou, Katherine A.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Hui, Jennie
    Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia;Sir Charles Gairdner Hosp, PathWest Lab Med WA, Crawley, WA, Australia;Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia.
    Karrasch, Stefan
    German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany;German Ctr Lung Res DZL, Comprehens Pneumol Ctr Munich, Munich, Germany.
    Imboden, Medea
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Marten, Jonathan
    Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Enroth, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kerr, Shona M.
    Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Surakka, Ida
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland;Natl Inst Hlth & Welf THL, Helsinki, Finland.
    Vitart, Veronique
    Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Fimlab Labs, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland.
    Ewert, Ralf
    Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany.
    Gieger, Christian
    German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
    Joshi, Peter K.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Med Res Council, Epidemiol Unit, Cambridge, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Luan, Jianan
    Univ Cambridge, Sch Clin Med, Med Res Council, Epidemiol Unit, Cambridge, England.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Murray, Alison
    Univ Aberdeen, Inst Med Sci, Aberdeen Biomed Imaging Ctr, Aberdeen, Scotland.
    Porteous, David J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Western Gen Hosp, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Rawal, Rajesh
    German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
    Smith, Blair H.
    Univ Dundee, Div Populat Hlth & Genom, Ninewells Hosp & Med Sch, Dundee, Scotland.
    Timmers, Paul R. H. J.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
    Kahonen, Mika
    Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Dept Clin Physiol, Tampere Univ Hosp, Tampere, Finland.
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Split, Sch Med, Split, Croatia.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
    Probst-Hensch, Nicole M.
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Schulz, Holger
    German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;German Ctr Lung Res DZL, Comprehens Pneumol Ctr Munich, Munich, Germany.
    James, Alan L.
    Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia;Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia.
    Wilson, James F.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Stubbe, Beate
    Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany.
    Zeggini, Eleftheria
    Wellcome Sanger Inst, Hinxton, England;German Res Ctr Environm Hlth, Inst Translat Genom, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England;Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland;Univ Oulu, Bioctr Oulu, Oulu, Finland;Oulu Univ Hosp, OYS, Unit Primary Hlth Care, Oulu, Finland;Brunel Univ London, Dept Life Sci, Coll Hlth & Life Sci, Uxbridge, Middx, England.
    Wareham, Nick
    Univ Cambridge, Sch Clin Med, Med Res Council, Epidemiol Unit, Cambridge, England.
    Hayward, Caroline
    Univ Edinburgh, Med Res Council, Inst Genet & Mol Med, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Agusti, Alvar
    Univ Barcelona, IDIBAPS, CIBERES, Resp Inst,Hosp Clin, Barcelona, Spain.
    Anderson, Wayne
    Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA.
    Bakerly, Nawar
    Salford Royal NHS Fdn Trust, Salford, Lancs, England;Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England.
    Bals, Robert
    Saarland Univ, Dept Internal Med Pulmonol Allergol & Crit Care 5, Homburg, Germany.
    Barnes, Kathleen C.
    Univ Colorado Denver, Dept Med, Sch Med, Aurora, CO USA.
    Bleecker, Eugene R.
    Univ Arizona, Dept Med, Tucson, AZ USA.
    Bowler, Russell
    Natl Jewish Hlth, Div Pulm & Crit Care Med, Dept Med, Denver, CO USA.
    Brightling, Christopher
    Glenfield Hosp, Natl Inst Hlth Res, Leicester Resp Biomed Res Ctr, Leicester, Leics, England;Univ Leicester, Dept Resp Med Allergy & Thorac Surg, Glenfield Hosp, Leicester, Leics, England.
    de Bruijne, Marleen
    Erasmus MC, Biomed Imaging Grp Rotterdam, Dept Radiol, Rotterdam, Netherlands;Erasmus MC, Biomed Imaging Grp Rotterdam, Dept Med Informat, Rotterdam, Netherlands;Univ Copenhagen, Dept Comp Sci, Copenhagen, Denmark.
    Castaldi, Peterj
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Celli, Bartolome
    Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Coxson, Harvey O.
    Univ British Columbia, Dept Radiol, Vancouver, BC, Canada.
    Crystal, Ron
    Weill Cornell Med Coll, Dept Genet Med, New York, NY USA;Weill Cornell Med Coll, Div Pulm & Crit Care Med, Dept Med, New York, NY USA.
    de Jong, Pim
    Univ Med Ctr Utrecht, Dept Resp Med, Utrecht, Netherlands.
    Dirksen, Asger
    Herlev & Gentofte Hosp, Dept Resp Med, Copenhagen, Denmark.
    Dy, Jennifer
    Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA.
    Foreman, Marilyn
    Morehouse Sch Med, Atlanta, GA 30310 USA.
    Garcia-Aymerich, Judith
    ISGlobal, Barcelona, Spain;Univ Pompeu Fabra, Barcelona, Spain;CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
    Gevenois, Pierre
    Univ Libre Bruxelles, Hop Erasme, Dept Radiol, Brussels, Belgium.
    Ghosh, Soumitra
    GlaxoSmithKline R&D, Collegeville, PA USA.
    Gietema, Hester
    Maastricht Univ, Med Ctr, Dept Radiol, Maastricht, Netherlands.
    Hansel, Nadia
    Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
    Hersh, Craig P.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Hoffman, Eric
    Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
    Kalsheker, Noor
    Univ Nottingham, Sch Life Sci, Nottingham, England.
    Kauczor, Hans-Ulrich
    Heidelberg Univ, Translat Lung Res Ctr Heidelberg, Dept Diagnost & Intervent Radiol, Heidelberg, Germany.
    Laitinen, Tarja
    Turku Univ Hosp, Univ Turku, Dept Pulm Dis & Clin Allergol, Turku, Finland.
    Lambrechts, Diether
    VIB, Vesalius Res Ctr VRC, Leuven, Belgium;Katholieke Univ Leuven, Lab Translat Genet, Dept Oncol, Leuven, Belgium.
    Litonjua, Augusto A.
    Univ Rochester, Med Ctr, Dept Pediat, Golisano Childrens Hosp Strong,Div Pediat Pulm Me, Rochester, NY 14642 USA.
    Loth, Daan W.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Lutz, Sharon M.
    Harvard Pilgr Hlth Care Inst, Dept Populat Med, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA.
    Lynch, David
    Natl Jewish Hlth, Dept Radiol, Denver, CO USA.
    MacNee, William
    Univ Edinburgh, Dept Resp Med, Edinburgh, Midlothian, Scotland.
    McDonald, Merry-Lynn
    Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA.
    Newell, John D.
    Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem & Copenhagen Gen Populat Study, Herlev, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Oh, Yeon-Mok
    Univ Ulsan Coll Med, Dept Pulm & Crit Care Med, Asan Med Ctr, Seoul, South Korea;Univ Ulsan Coll Med, Clin Res Ctr Chron Obstruct Airway Dis, Seoul, South Korea.
    Pare, Peter D.
    Univ British Columbia, Ctr Heart Lung Innovat, St Pauls Hosp, Vancouver, BC, Canada;Univ British Columbia, St Pauls Hosp, Inst Heart & Lung Hlth, Dept Med, Vancouver, BC, Canada.
    Pistolesi, Massimo
    Univ Hosp Careggi, Dept Clin & Expt Med, Florence, Italy.
    Postma, Dirkje S.
    Univ Groningen, Univ Med Ctr Groningen, GRIAC, Groningen, Netherlands.
    Puhan, Milo
    Univ Zurich, Epidemiol Biostat & Prevent Inst, Zurich, Switzerland.
    Regan, Elizabeth
    Natl Jewish Hlth, Div Rheumatol, Dept Med, Denver, CO USA.
    Rich, Stephen S.
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Seo, Joon Beom
    Univ Ulsan, Asan Med Ctr, Dept Radiol, Coll Med, Seoul, South Korea;Univ Ulsan, Asan Med Ctr, Res Inst Radiol, Coll Med, Seoul, South Korea.
    Short, Andrea
    Univ Manchester, Sch Social Sci, Manchester, Lancs, England.
    Stoel, Berend
    Leiden Univ, Med Ctr, Leiden, Netherlands.
    Sverzellati, Nicola
    Univ Parma, Dept Med & Surg, Radiol, Parma, Italy.
    ter Riet, Gerben
    Univ Amsterdam, Acad Med Ctr, Dept Gen Practice, Amsterdam, Netherlands.
    Van Beek, Edwin J. R.
    Univ Edinburgh, Edinburgh Imaging, Edinburgh, Midlothian, Scotland.
    Van Ginneken, Bram
    Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, Nijmegen, Netherlands.
    Vogelmeier, Claus F.
    Univ Marburg, Pulm Dis, Marburg, Germany.
    Wanner, Adam
    Univ Miami, Miller Sch Med, Dept Med, Div Pulm Allergy Crit Care & Sleep Med, Miami, FL 33136 USA.
    Washko, George
    Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
    Wauters, Els
    Katholieke Univ Leuven, Lab Pneumol, Dept Chron Dis Metab & Ageing, Leuven, Belgium.
    Wouters, Emiel F. M.
    Maastricht Univ, Resp Med, Med Ctr, Maastricht, Netherlands.
    Young, Robert P.
    Univ Auckland, Sch Biol Sci, Auckland, New Zealand;Univ Auckland, Fac Med & Hlth Sci, Auckland, New Zealand.
    Zeigler-Heitbrock, Loems
    Helmholtz Zentrum Munchen, EvA Study Ctr, Gauting, Germany.
    Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 494-505Article in journal (Refereed)
    Abstract [en]

    Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.

  • 39.
    Shrine, Nick
    et al.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Guyatt, Anna L.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Erzurumluoglu, A. Mesut
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Jackson, Victoria E.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Parkville, Vic, Australia;Univ Melbourne, Dept Med Biol, Parkville, Vic, Australia.
    Hobbs, Brian D.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Melbourne, Carl A.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Batini, Chiara
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Fawcett, Katherine A.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Song, Kijoung
    GlaxoSmithKline, Target Sci, Collegeville, PA USA.
    Sakornsakolpat, Phuwanat
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Mahidol Univ, Fac Med, Dept Med, Siriraj Hosp, Bangkok, Thailand.
    Li, Xingnan
    Univ Arizona, Dept Med, Div Genet Genom & Precis Med, Tucson, AZ USA.
    Boxall, Ruth
    Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Med Res Council, Populat Hlth Res Unit, Oxford, England.
    Reeve, Nicola F.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Obeidat, Ma'en
    Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
    Zhao, Jing Hua
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England.
    Wielscher, Matthias
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
    Weiss, Stefan
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
    Kentistou, Katherine A.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Cardiovasc Sci, Queens Med Res Inst, Edinburgh, Midlothian, Scotland.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Sun, Benjamin B.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Zhou, Jian
    Simons Fdn, Flatiron Inst, New York, NY USA.
    Hui, Jennie
    Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Univ Western Australia, Sch Populat Hlth, Crawley, WA, Australia;Sir Charles Gairdner Hosp, PathWest Lab Med WA, Crawley, WA, Australia;Univ Western Australia, Sch Pathol & Lab Med, Crawley, WA, Australia.
    Karrasch, Stefan
    Helmholtz Zentrum Muenchen, Inst Epidemiol, German Res Ctr Environ, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany;CPC M, Munich, Germany.
    Imboden, Medea
    German Ctr Lung Res DZL, Munich, Germany;Swiss Trop & Publ Hlth Inst, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kerr, Shona M.
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Surakka, Ida
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland;Natl Inst Hlth & Welf THL, Helsinki, Finland.
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Lehtimaki, Terho
    Univ Tampere, Dept Clin Chem, Fimlab Labs, Tampere, Finland;Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland.
    Allen, Richard J.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Bakke, Per S.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Beaty, Terri H.
    Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
    Bleecker, Eugene R.
    Univ Arizona, Dept Med, Div Genet Genom & Precis Med, Tucson, AZ USA.
    Bosse, Yohan
    Laval Univ, Dept Mol Med, Quebec City, PQ, Canada;Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Brandsma, Corry-Anke
    Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Pathol & Med Biol, Groningen, Netherlands.
    Chen, Zhengming
    Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
    Crapo, James D.
    Natl Jewish Hlth, Denver, CO USA;Natl Jewish Hlth, Div Pulm Crit Care & Sleep Med, Denver, CO USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;British Heart Fdn Cambridge Ctr Excellence, Addenbrookes Hosp, Div Cardiovasc Med, Cambridge, England;Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    DeMeo, Dawn L.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Dudbridge, Frank
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Ewert, Ralf
    Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany.
    Gieger, Christian
    German Res Ctr Environ, Inst Epidemiol, Res Unit Mol Epidemiol, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
    Gulsvik, Amund
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Hansell, Anna L.
    Univ Leicester, Ctr Environm Hlth & Sustainabil, Leicester, Leics, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, UK Small Area Hlth Stat Unit, London, England;Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England.
    Hao, Ke
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Hoffman, Joshua D.
    GlaxoSmithKline, Target Sci, Collegeville, PA USA.
    Hokanson, John E.
    Univ Colorado, Dept Epidemiol, Anschutz Med Campus, Aurora, CO USA.
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
    Joshi, Peter K.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Joubert, Philippe
    Laval Univ, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada;Laval Univ, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada.
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge, England.
    Li, Xuan
    Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
    Li, Liming
    Peking Univ, Dept Epidemiol & Biostat, Hlth Sci Ctr, Beijing, Peoples R China.
    Lin, Kuang
    Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Locantore, Nicholas
    GlaxoSmithKline Res & Dev Ltd, Collegeville, PA USA.
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge, England.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Maranville, Joseph C.
    Merck & Co Inc, MRL, Kenilworth, NJ USA.
    Murray, Alison
    Univ Aberdeen, Aberdeen Biomed Imaging Ctr, Inst Med Sci, Aberdeen, Scotland.
    Nickle, David C.
    Merck & Co Inc, MRL, Kenilworth, NJ USA;Gossamer Bio, San Diego, CA USA.
    Packer, Richard
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Parker, Margaret M.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Paynton, Megan L.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
    Porteous, David J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Prokopenko, Dmitry
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Qiao, Dandi
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
    Rawal, Rajesh
    German Res Ctr Environ, Inst Epidemiol, Res Unit Mol Epidemiol, Helmholtz Zentrum Muenchen, Neuherberg, Germany;Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
    Runz, Heiko
    Merck & Co Inc, MRL, Kenilworth, NJ USA.
    Sayers, Ian
    Univ Nottingham, Div Resp Med & NIHR Nottingham Biomed Res Ctr, Nottingham, England.
    Sin, Don D.
    Univ British Columbia, St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada;Univ British Columbia, Dept Med, Resp Div, Vancouver, BC, Canada.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp, Div Populat Hlth & Genom, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland.
    Artigas, Maria Soler
    Univ Autonoma Barcelona, Vail dHebron Res Inst VHIR, Psychiat Genet Unit, Grp Psychiat Mental Hlth & Addict, Barcelona, Spain;Hosp Univ Vall Hebron, Dept Psychiat, Barcelona, Spain;Inst Salud Carlos III, Biomed Network Res Ctr Mental Hlth CIBERSAM, Barcelona, Spain.
    Sparrow, David
    VA Boston Healthcare Syst, Boston, MA USA;Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
    Tal-Singer, Ruth
    GlaxoSmithKline Res & Dev Ltd, Collegeville, PA USA.
    Timmers, Paul R. H. J.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Van den Berge, Maarten
    Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, GRIAC Res Inst, Groningen, Netherlands.
    Whittaker, John C.
    Target Sci R&D, GSK Med Res Ctr, Stevenage, Herts, England.
    Woodruff, Prescott G.
    Univ Calif San Francisco, UCSF Pulm Crit Care Allergy & Sleep Med, San Francisco, CA USA.
    Verges-Armstrong, Laura M.
    GlaxoSmithKline, Target Sci, Collegeville, PA USA.
    Troyanskaya, Olga G.
    Princeton Univ, Dept Comp Sci, Princeton, NJ 08544 USA;Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
    Kahonenn, Mika
    Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Dept Clin Physiol, Tampere Univ Hosp, Fac Med & Life Sci, Tampere, Finland.
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Split Sch Med, Split, Croatia.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
    Probst-Hensch, Nicole M.
    German Ctr Lung Res DZL, Munich, Germany;Swiss Trop & Publ Hlth Inst, Basel, Switzerland;Univ Basel, Basel, Switzerland.
    Schulz, Holger
    Helmholtz Zentrum Muenchen, Inst Epidemiol, German Res Ctr Environ, Neuherberg, Germany;CPC M, Munich, Germany.
    James, Alan L.
    Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA, Australia;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia;Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia.
    Wilson, James F.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Stubbe, Beate
    Univ Med Greifswald, Dept Internal Med B Cardiol Intens Care Pulm Med, Greifswald, Germany.
    Zeggini, Eleftheria
    Wellcome Sanger Inst, Hinxton, England;German Res Ctr Environ, Inst Translat Genom, Helmholtz Zentrum Muenchen, Neuherberg, Germany.
    Jarvelin, Marjo-Riitta
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England;Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland;Univ Oulu, Bioctr Oulu, Oulu, Finland;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland;Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, Uxbridge, Middx, England.
    Wareham, Nick
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Cambridge, England.
    Silverman, Edwin K.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Scott, Robert A.
    Target Sci R&D, GSK Med Res Ctr, Stevenage, Herts, England.
    Walters, Robin G.
    Univ Oxford, Nuffield Dept Populat Hlth, Oxford, England.
    Meyers, Deborah A.
    Univ Arizona, Dept Med, Div Genet Genom & Precis Med, Tucson, AZ USA.
    Cho, Michael H.
    Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England.
    Hall, Ian P.
    Univ Nottingham, Div Resp Med & NIHR Nottingham Biomed Res Ctr, Nottingham, England.
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, Leicester Resp Biomed Res Ctr, Natl Inst Hlth Res, Leicester, Leics, England.
    Wain, Louise, V
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England;Glenfield Hosp, Leicester Resp Biomed Res Ctr, Natl Inst Hlth Res, Leicester, Leics, England.
    New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 481-493Article in journal (Refereed)
    Abstract [en]

    Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.

  • 40.
    Sjöholm, Therese
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekström, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    A whole-body FDG PET/MR atlas for multiparametric voxel-based analysis2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 6158Article in journal (Refereed)
  • 41.
    Spracklen, Cassandra N.
    et al.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus;Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark;Tech Univ Denmark, DTU Hlth Technol, DK-2800 Lyngby, Denmark.
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Westminster, Sch Life Sci, Res Ctr Optimal Hlth, London, England.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Fine, Rebecca S.
    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Kutalik, Zoltan
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England;Univ Lausanne, Univ Ctr Primary Care & Publ Hlth, CH-1010 Lausanne, Switzerland;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med,Sch Med, Nashville, TN 37203 USA;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
    Wittemans, Laura B. L.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Adair, Linda S.
    Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC 27516 USA.
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92093 USA.
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Auer, Paul L.
    Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
    Bartz, Traci M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA;Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Blueher, Matthias
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Borja, Judith B.
    Off Populat Studies Fdn Inc, Cebu, Philippines;Univ San Carlos, Dept Nutr & Dietet, Cebu, Philippines.
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Broer, Linda
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Chirstofidou, Paraskevi
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Demirkan, Ayse
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Garcia, Melissa E.
    NHLBI, Bldg 10, Bethesda, MD 20892 USA.
    Graff, Mariaelisa
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA;Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
    Grallert, Harald
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Haesser, Jeffrey
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA.
    Highland, Heather M.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Hong, Jaeyoung
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Cardiovasc Inst, Palo Alto, CA 94304 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Jackson, Rebecca
    Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere 33522, Finland.
    Kizer, Jorge R.
    Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
    Kovacs, Peter
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70029, Kys, Finland;Kuopio Univ Hosp, Kuopio 70029, Kys, Finland.
    Lange, Leslie A.
    Univ Colorado, Dept Med, Div Biomed Informat & Personalized Med, Denver, CO 80045 USA.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33522, Finland.
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94304 USA.
    Li-Gao, Ruifang
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33522, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33521, Finland.
    MacGregor, Stuart
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
    Mackey, David A.
    Univ Western Australia, Fac Hlth & Med Sci, Perth, WA 6009, Australia;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England;Guys & St Thomas Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7FZ, England.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Medina-Gomez, Carolina
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Broad Inst, Program Populat & Med Genet, Cambridge, MA 02114 USA.
    Molnos, Sophie
    Helmholtz Zentrum Munchen, Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, D-85764 Munich, Germany;German Ctr Diabet Res, D-85765 Munich, Germany.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2334 ZA Leiden, Netherlands.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2333 ZA Leiden, Netherlands.
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD 20812 USA.
    Nedeljkovic, Ivana
    Erasmus MC, Dept Epidemiol, NL-3015 CN Rotterdam, Netherlands.
    North, Kari E.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Pennell, Craig E.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Pradhan, Aruna D.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Raitakari, Olli T.
    Univ Turku, Ctr Populat Hlth Res, Turku, Finland;Turku Univ Hosp, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
    Raulerson, Chelsea K.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Ripatti, Samuli
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Helsinki, Publ Hlth, FIN-00014 Helsinki, Finland;Inst Mol Med Finland, Helsinki 00014, Finland.
    Roberston, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7FZ, England.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki 00271, Finland.
    Sandoval-Zarate, America A.
    Inst Mol Med Finland, Helsinki 00014, Finland.
    Sitlani, Colleen M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, D-85764 Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.
    Stumvoll, Michael
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Thuesen, Betina
    Capital Reg, Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Dis Prevent, DK-2400 Copenhagen, Denmark.
    Toenjes, Anke
    Univ Leipzig, Med Dept Endocrinol Nephrol Rheumatol 3, Leipzig, Germany.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands.
    Venturini, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
    Wang, Carol A.
    Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW 2305, Australia.
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Willems, Sara M.
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    van Dijk, Ko Willems
    Leiden Univ, Med Ctr, Div Endocrinol, Dept Internal Med, NL-2333 ZA Leiden, Netherlands;Einthoven Lab Expt Vasc Med, NL-2333 ZA Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
    Young, Kristin L.
    Univ North Carolina Chapel Hill, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Cambridge CB2 0QQ, England.
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Royal Devon & Exeter Hosp, Genet Complex Traits, Exeter EX2 5DW, Devon, England.
    Kilpelainen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2200 Copenhagen, Denmark;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7FZ, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA;Univ Oxford, Nuffield Dept Med, Big Data Inst, Oxford OX3 7LF, England.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
    Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology2019In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 105, no 1, p. 15-28Article in journal (Refereed)
    Abstract [en]

    Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 x 10(-7)). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r(2) > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 x 10(-4)) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

  • 42.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Björkelund, Cecilia
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Primary Hlth Care, Gothenburg, Sweden.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hansson, Per-Olof
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Högman, Marieann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Koupil, Ilona
    Stockholm Univ, Dept Publ Hlth Sci, Stockholm, Sweden;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
    Kristenson, Margareta
    Linkoping Univ, Dept Med & Hlth Sci, Div Community Med, Linkoping, Sweden.
    Lagerros, Ylva Trolle
    Karolinska Inst, Dept Med, Unit Clin Epidemiol, Stockholm, Sweden;Karolinska Univ Hosp Huddinge, Dept Endocrinol Metab & Diabet, Huddinge, Sweden.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lissner, Lauren
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med Epidemiol & Social, Gothenburg, Sweden.
    Johansson, Ingegerd
    Umea Univ, Sch Dent, Dept Odontol, Umea, Sweden.
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Orebro Univ, Orebro Univ Hosp, Dept Pediat, Orebro, Sweden.
    Nilsson, Peter M.
    Skane Univ Hosp, Dept Clin Sci, Malmo, Sweden;Lund Univ, Lund, Sweden.
    Olsson, Håkan
    Lund Univ, Dept Clin Sci Canc Epidemiol, Lund, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Karlsson, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Rosengren, Annika
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Sandin, Sven
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA;Seaver Autism Ctr Res & Treatment Mt Sinai, New York, NY USA.
    Snäckerström, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stenbeck, Magnus
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Umea Univ, Heart Ctr, Umea, Sweden.
    Weiderpass, Elisabete
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden;Inst Populat Based Canc Res, Dept Res, Canc Registry Norway, Oslo, Norway;Univ Helsinki, Fac Med, Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland;Univ Tromso, Arctic Univ Norway, Dept Community Med, Tromso, Norway.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wennberg, Patrik
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Fortier, Isabel
    McGill Univ, Res Inst, Hlth Ctr, Montreal, PQ, Canada.
    Heller, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storgärds, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rationale for a Swedish cohort consortium2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 21-28Article in journal (Refereed)
    Abstract [en]

    We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.

  • 43.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nowrouzi, Shamim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Marttala, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekman, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 51-58Article in journal (Refereed)
    Abstract [en]

    High blood pressure is the leading risk factor for premature deaths and a major cost to societies worldwide. Effective blood pressure-lowering drugs are available, but patient adherence to them is low, likely partly due to side effects. To identify patient-specific differences in treatment effects, a repeated cross-over design, where the same treatment contrasts are repeated within each patient, is needed. Such designs have been surprisingly rarely used, given the current focus on precision medicine. The Precision HYpertenSIon Care (PHYSIC) study aims to investigate if there is a consistent between-person variation in blood pressure response to the common blood pressure-lowering drug classes of a clinically relevant magnitude, given the within-person variation in blood pressure. The study will also investigate the between-person variation in side effects of the drugs. In a double-blind, randomized, repeated cross-over trial, 300 patients with mild hypertension will be treated with four blood pressure-lowering drugs (candesartan, lisinopril, amlodipine, and hydrochlorothiazide) in monotherapy, with two of the drugs repeated for each patient. If the study indicates that there is a potential for precision hypertension care, the most promising predictors of blood pressure and side effect response to the drugs will be explored, as will the potential for development of a biomarker panel to rank the suitability of blood pressure-lowering drug classes for individual patients in terms of anticipated blood pressure effects and side effects, with the ultimate goal to maximize adherence. The study follows a protocol pre-registered at ClinicalTrials.gov with the identifier NCT02774460.

  • 44.
    Tan, Xiao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Titova, Olga E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Elmståhl, Sölve
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association Between Self-Reported Sleep Duration and Body Composition in Middle-Aged and Older Adults2019In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 15, no 3, p. 431-435Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: The current study sought to examine whether self-reported sleep duration is linked to an adverse body composition in 19,709 adults aged 45 to 75 years.

    METHODS: All variables used in the current study were derived from the Swedish EpiHealth cohort study. Habitual sleep duration was measured by questionnaires. Body composition was assessed by bioimpedance. The main outcome variables were fat mass and fat-free mass (in kg). Analysis of covariance adjusting for age, sex, fat mass in the case of fat-free mass (and vice versa), leisure time physical activity, smoking, and alcohol consumption was used to investigate the association between sleep duration and body composition.

    RESULTS: Short sleep (defined as ≤ 5 hours sleep per day) and long sleep (defined as 8 or more hours of sleep per day) were associated with lower fat-free mass and higher fat mass, compared with 6 to 7 hours of sleep duration (P< .05).

    CONCLUSIONS: These observations could suggest that both habitual short and long sleep may contribute to two common clinical phenotypes in middle-aged and older humans, ie, body adiposity and sarcopenia. However, the observational nature of our study does not allow for causal interpretation.

  • 45.
    Wagner-Golbs, Antje
    et al.
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Neuber, Sebastian
    Biocrates Life Sci AG, Eduard Bodem Gasse 8, A-6020 Innsbruck, Austria.
    Kamlage, Beate
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Christiansen, Nicole
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Bethan, Bianca
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Rennefahrt, Ulrike
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Schatz, Philipp
    Metan Hlth GmbH, Tegeler Weg 33, D-10589 Berlin, Germany.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Effects of Long-Term Storage at -80 degrees C on the Human Plasma Metabolome2019In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 9, no 5, article id 99Article in journal (Refereed)
    Abstract [en]

    High-quality biological samples are required for the favorable outcome of research studies, and valid data sets are crucial for successful biomarker identification. Prolonged storage of biospecimens may have an artificial effect on compound levels. In order to investigate the potential effects of long-term storage on the metabolome, human ethylenediaminetetraacetic acid (EDTA) plasma samples stored for up to 16 years were analyzed by gas and liquid chromatography-tandem mass spectrometry-based metabolomics. Only 2% of 231 tested plasma metabolites were altered in the first seven years of storage. However, upon longer storage periods of up to 16 years and more time differences of few years significantly affected up to 26% of the investigated metabolites when analyzed within subject age groups. Ontology classes that were most affected included complex lipids, fatty acids, energy metabolism molecules, and amino acids. In conclusion, the human plasma metabolome is adequately stable to long-term storage at -80 degrees C for up to seven years but significant changes occur upon longer storage. However, other biospecimens may display different sensitivities to long-term storage. Therefore, in retrospective studies on EDTA plasma samples, analysis is best performed within the first seven years of storage.

  • 46.
    Wuttke, Matthias
    et al.
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany;Univ Freiburg, Fac Med, Dept Med 4, Renal Div, Freiburg, Germany.
    Li, Yong
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Li, Man
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Sieber, Karsten B.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Gorski, Mathias
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA;Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
    Wang, Lihua
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Chu, Audrey Y.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Hoppmann, Anselm
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Kirsten, Holger
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Giri, Ayush
    Vanderbilt Univ, Med Ctr,Div Quantitat Sci, Dept Obstet & Gynecol,Vanderbilt Genet Inst, Inst Med & Publ Hlth,Vanderbilt Epidemiol Ctr, Nashville, TN 37232 USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Biomed Lab Res & Dev, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Chai, Jin-Fang
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Sveinbjornsson, Gardar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Tayo, Bamidele O.
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA.
    Nutile, Teresa
    Adriano Buzzati Traverso CNR, Inst Genet & Biophys, Naples, Italy.
    Fuchsberger, Christian
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Cocca, Massimiliano
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Ghasemi, Sahar
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Xu, Yizhe
    Univ Utah, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84112 USA.
    Horn, Katrin
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Noce, Damia
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Sedaghat, Sanaz
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Yu, Zhi
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
    Akiyama, Masato
    RIKEN, Ctr Integrat Med Sci IMS, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Fukuoka, Fukuoka, Japan.
    Afaq, Saima
    Imperial Coll London, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England;Khyber Med Univ, Inst Publ Hlth & Social Sci, Peshawar, Pakistan.
    Ahluwalia, Tarunveer S.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Almgren, Peter
    Lund Univ, Dept Clincial Sci Malmo, Diabetes & Cardiovasc Disease Genet Epidemi, Malmo, Sweden.
    Amin, Najaf
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, Stockholm, Sweden;Dalarna Univ, Sch Hlth & Social Studies, Stockholm, Sweden.
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    Bansal, Nisha
    Univ Washington, Div Nephrol, Seattle, WA 98195 USA;Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
    Baptista, Daniela
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland;Univ Cape Town, Dept Integrat Biomed Sci, Cape Town, South Africa.
    Biggs, Mary L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Biino, Ginevra
    Natl Res Council Italy, Inst Mol Genet, Pavia, Italy.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Boissel, Mathilde
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, Lille, France.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Hasso Plattner Inst, Digital Hlth Ctr, Potsdam, Germany;Univ Potsdam, Potsdam, Germany.
    Boutin, Thibaud S.
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Brenner, Hermann
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany;Heidelberg Univ, Network Aging Res, Heidelberg, Germany.
    Brumat, Marco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Burkhardt, Ralph
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany;Univ Hosp Regensburg, Inst Clin Chem & Lab Med, Regensburg, Germany.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Res Unit Do, Cambridge, England.
    Campana, Eric
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Canouil, Mickael
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, Lille, France.
    Carroll, Robert J.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Catamo, Eulalia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Ealing Gen Hosp, Dept Cardiol, Middlesex, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
    Chee, Miao-Ling
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chee, Miao-Li
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Chen, Xu
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Cheng, Ching-Yu
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Cheng, Yurong
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Christensen, Kaare
    Southern Denmark Univ, Dept Publ Hlth, Unit Epidemiol Biostat & Biodemog, Odense, Denmark.
    Cifkova, Renata
    Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic;Thomayer Hosp, Prague, Czech Republic;Charles Univ Prague, Fac Med 1, Dept Med 2, Prague, Czech Republic.
    Ciullo, Marina
    Adriano Buzzati Traverso CNR, Inst Genet & Biophys, Naples, Italy;IRCCS Neuromed, Pozzilli, Italy.
    Concas, Maria Pina
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
    Corre, Tanguy
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland;Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.
    Sala, Cinzia Felicita
    San Raffaele Res Inst, Milan, Italy.
    Cusi, Daniele
    Natl Res Council Italy, Inst Biomed Technol, Milan, Italy;Bio4Dreams Business Nursery Life Sci, Milan, Italy.
    Danesh, John
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    Daw, E. Warwick
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    De Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    De Grandi, Alessandro
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    De Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    De Vries, Aiko P. J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands.
    Degenhardt, Frauke
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med, Nephrol,Hypertensiol,Rheumatol,Endocrinol,Diabet, Mannheim, Germany.
    Demirkan, Ayse
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England;NHS Blood & Transplant, Cambridge, England.
    Dittrich, Katalin
    Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Divers, Jasmin
    Wake Forest Sch Med, Publ Hlth Sci Biostat, Winston Salem, NC USA.
    Dorajoo, Rajkumar
    Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
    Eckardt, Kai-Uwe
    Charite, Intens Care Med, Berlin, Germany;Friedrich Alexander Univ Erlangen Nurnberg FAU, Dept Nephrol & Hypertens, Erlangen, Germany.
    Ehret, Georg
    Geneva Univ Hosp, Cardiol, Geneva, Switzerland.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England;Imperial Coll London, Imperial Coll, NIHR Biomed Res Ctr, London, England;Imperial Coll London, Dementia Res Inst, London, England;Hlth Data Res UK London, London, England.
    Endlich, Karlhans
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Anat & Cell Biol, Greifswald, Germany.
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
    Felix, Janine F.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Foo, Valencia Hui Xian
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Bern, ISPM, Bern, Switzerland.
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
    Freedman, Barry I.
    Wake Forest Sch Med, Internal Med, Sect Nephrol, Winston Salem, NC USA.
    Freitag-Wolf, Sandra
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Friedlander, Yechiel
    Hebrew Univ Jerusalem, Sch Publ Hlth & Community Med, Jerusalem, Israel.
    Froguel, Philippe
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, Lille, France;Imperial Coll London, Dept Genom Common Dis, London, England.
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands.
    Gao, He
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
    Gasparini, Paolo
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Gaziano, J. Michael
    VA Boston Healthcare Syst, VA Cooperat Studies Program, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gieger, Christian
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Girotto, Giorgia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy.
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Gogele, Martin
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Gudbjartsson, Daniel F.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Haller, Toomas
    Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
    Hamet, Pavel
    CHUM, Montreal Univ Hosp, Res Ctr, Montreal, PQ, Canada;Medpharmgene, Montreal, PQ, Canada.
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US NIH, Bethesda, MD 20892 USA.
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, nterdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Hellwege, Jacklyn N.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA;Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol,Vanderbilt Genet Inst, Nashville, TN 37232 USA;Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Heng, Chew-Kiat
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore;Natl Univ Hlth Syst, Khoo Teck Puat Natl Univ, Childrens Med Inst, Singapore, Singapore.
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Hofer, Edith
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria.
    Huang, Wei
    Chinese Natl Human Genome Ctr, Shanghai MOST Key Lab Hlth & Dis Genom, Dept Genet, Shanghai, Peoples R China;Shanghai Ind Technol Inst, Shanghai, Peoples R China.
    Hutri-Kahonen, Nina
    Tampere Univ Hosp, Dept Pediat, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Dept Pediat, Tampere, Finland.
    Hwang, Shih-Jen
    NHLBIs Framingham Heart Study, Framingham, MA USA;NHLBI, Ctr Populat Studies, Framingham, MA USA.
    Ikram, M. Arfan
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Indridason, Olafur S.
    Natl Univ Hosp Iceland, Landspitali, Internal Med Serv, Div Nephrol, Reykjavik, Iceland.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Ising, Marcus
    Max Planck Inst Psychiat, Munich, Germany.
    Jaddoe, Vincent W. V.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic;Thomayer Hosp, Prague, Czech Republic;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Jakobsdottir, Johanna
    Univ Iceland, Ctr Publ Hlth Sci, Reykjavik, Iceland.
    Jonas, Jost B.
    Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany;Capital Med Univ, Beijing Tongren Hosp, Beijing Key Lab Ophthalmol & Visual Sci, Beijing Inst Ophthalmol, Beijing, Peoples R China.
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Josyula, Navya Shilpa
    Biomed & Translat Informat Inst, Geisinger Res, Rockville, MD USA.
    Jung, Bettina
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland;Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Physiol, Tampere, Finland.
    Kamatani, Yoichiro
    RIKEN, Ctr Integrat Med Sci IMS, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyoto Univ, Grad Sch Med, Kyoto McGill Int Collaborat Sch Genom Med, Kyoto, Japan.
    Kammerer, Candace M.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
    Kanai, Masahiro
    RIKEN, Ctr Integrat Med Sci IMS, Lab Stat Anal, Yokohama, Kanagawa, Japan;Harvard Med Sch, Dept Biomed Informat, Boston, MA 02115 USA.
    Kastarinen, Mika
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland.
    Kerr, Shona M.
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Khor, Chiea-Chuen
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.
    Kiess, Wieland
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med, Nephrol,Hypertensiol,Rheumatol,Endocrinol,Diabet, Mannheim, Germany.
    Koenig, Wolfgang
    Tech Univ Munich, Deutsches Herzzentrum Munchen, Munich, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Univ Ulm, Inst Epidemiol & Biostat, Ulm, Germany.
    Kooner, Jaspal S.
    Ealing Gen Hosp, Dept Cardiol, Middlesex, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England;Imperial Coll London, Natl Heart & Lung Inst, London, England.
    Korner, Antje
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Hosp Children & Adolescents, Dept Women & Child Hlth, Leipzig, Germany;Univ Leipzig, Ctr Pediat Res, Leipzig, Germany.
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment Ctr Adipos Dis, Leipzig, Germany.
    Kraja, Aldi T.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Krajcoviechova, Alena
    Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic;Thomayer Hosp, Prague, Czech Republic;Charles Univ Prague, Fac Med 1, Dept Med 2, Prague, Czech Republic.
    Kramer, Holly
    Loyola Univ Chicago, Dept Publ Hlth Sci, Maywood, IL USA;Loyola Univ, Div Nephrol & Hypertens, Chicago, IL 60611 USA.
    Kramer, Bernhard K.
    Heidelberg Univ, Med Fac Mannheim, Dept Med, Nephrol,Hypertensiol,Rheumatol,Endocrinol,Diabet, Mannheim, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Kubo, Michiaki
    RIKEN, Ctr Integrat Med Sci IMS, Yokohama, Kanagawa, Japan.
    Kuhnel, Brigitte
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Kuokkanen, Mikko
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki, Finland;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland.
    Kuusisto, Johanna
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland;Univ Eastern Finland, Internal Med, Inst Clin Med, Kuopio, Finland.
    La Bianca, Martina
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Laakso, Markku
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland;Univ Eastern Finland, Internal Med, Inst Clin Med, Kuopio, Finland.
    Lange, Leslie A.
    Univ Colorado Denver, Sch Med, Div Biomed Informat & Personalized Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Publ Hlth Sci Biostat, Winston Salem, NC USA.
    Lee, Jeannette Jen-Mai
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Lehne, Benjamin
    Imperial Coll London, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England.
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany.
    Lim, Su-Chi
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Khoo Teck Puat Hosp, Diabet Ctr, Singapore, Singapore.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Oxford, England;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Liu, Jun
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Liu, Jianjun
    Natl Univ Hlth Syst, Singapore, Singapore;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.
    Loeffler, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Lucae, Susanne
    Max Planck Inst Psychiat, Munich, Germany.
    Lukas, Mary Ann
    GlaxoSmithKline, Target Sci Genet, Albuquerque, NM USA.
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Magi, Reedik
    Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Martins, Jade
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.
    Marz, Winfried
    Synlab Holding Deutschland GmbH, Synlab Acad, Mannheim, Germany;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria;Heidelberg Univ, Med Fac Mannheim, Med Clin 5, Mannheim, Germany.
    Mascalzoni, Deborah
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Matsuda, Koichi
    Univ Tokyo, Grad Sch Frontier Sci, Lab Clin Genome Sequencing, Tokyo, Japan.
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Independent Res Grp Clin Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, UNIKA T Augsburg, Chair Epidemiol, Augsburg, Germany.
    Meitinger, Thomas
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany;Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;Tech Univ Munich, Inst Human Genet, Munich, Germany.
    Melander, Olle
    Lund Univ, Dept Clincial Sci Malmo, Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Metspalu, Andres
    Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia.
    Mikaelsdottir, Evgenia K.
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Milaneschi, Yuri
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
    Miliku, Kozeta
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Mishra, Pashupati P.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Program, V. A. Million Veteran
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere, Finland.
    Montgomery, Grant W.
    Univ Queensland, Inst Mol Biosci, St Lucia, Qld, Australia.
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Mychaleckyj, Josyf C.
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Nadkarni, Girish N.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA;Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Nalls, Mike A.
    NIA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
    Nikus, Kjell
    Tampere Univ Hosp, Heart Ctr, Dept Cardiol, Tampere, Finland;Tampere Univ, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Cardiol, Tampere, Finland.
    Ning, Boting
    Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Noordam, Raymond
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Gerontol & Geriatr, Leiden, Netherlands.
    O'Connell, Jeffrey
    Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA;TIMI Study Grp, Boston, MA USA.
    Olafsson, Isleifur
    Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland.
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, nterdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands.
    Orho-Melander, Marju
    Lund Univ, Dept Clincial Sci Malmo, Diabetes & Cardiovasc Disease Genet Epidemi, Malmo, Sweden.
    Ouwehand, Willem H.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England.
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Palmer, Nicholette D.
    Wake Forest Sch Med, Biochem, Winston Salem, NC USA.
    Palsson, Runolfur
    Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland;Natl Univ Hosp Iceland, Landspitali, Internal Med Serv, Div Nephrol, Reykjavik, Iceland.
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
    Perls, Thomas
    Boston Univ, Sch Med, Dept Med, Geriatr Sect,Boston Med Ctr, Boston, MA 02118 USA.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Pirastu, Mario
    UOS Sassari, Natl Res Council Italy, Inst Genet & Biomed Res, Sassari, Italy.
    Pirastu, Nicola
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Pistis, Giorgio
    Univ Hosp Lausanne, Dept Psychiat, Lausanne, Switzerland.
    Podgornaia, Anna I.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Polasek, Ozren
    Univ Split, Fac Med, Split, Croatia;Gen Info Ltd, Zagreb, Croatia.
    Ponte, Belen
    Geneva Univ Hosp, Serv Nephrol, Geneva, Switzerland.
    Porteous, David J.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Poulain, Tanja
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Pramstaller, Peter P.
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Prins, Bram P.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Rabelink, Ton J.
    Leiden Univ, Med Ctr, Dept Internal Med, Sect Nephrol, Leiden, Netherlands;Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Res, Leiden, Netherlands.
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
    Reilly, Dermot F.
    Merck & Co Inc, Genet, Kenilworth, NJ USA.
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany.
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany.
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Rivadeneira, Fernando
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Rizzi, Federica
    Univ Milan, Dept Hlth Sci, Milan, Italy;ePhood SRL, ePhood Sci Unit, Milan, Italy.
    Roberts, David J.
    BRC Oxford Haematol Theme, NHS Blood & Transplant, Oxford, England;Nuffield Div Clin Lab Sci, Oxford, England;Univ Oxford, Oxford, England.
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy.
    Rossing, Peter
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Rueedi, Rico
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland;Swiss Inst Bioinformat, Lausanne, Switzerland.
    Ruggiero, Daniela
    Adriano Buzzati Traverso CNR, Inst Genet & Biophys, Naples, Italy;IRCCS Neuromed, Pozzilli, Italy.
    Ryan, Kathleen A.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
    Saba, Yasaman
    Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling Metab & A, Mol Biol & Biochem, Graz, Austria.
    Sabanayagam, Charumathi
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Salvi, Erika
    Univ Milan, Dept Hlth Sci, Milan, Italy;Fdn IRCCS Ist Neurol Carlo Besta, Neuroalgol Unit, Milan, Italy.
    Saum, Kai-Uwe
    German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
    Schmidt, Helena
    Med Univ Graz, Inst Mol Biol & Biochem, Ctr Mol Med, Graz, Austria.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.
    Schottker, Ben
    Schulz, Christina-Alexandra
    Lund Univ, Dept Clincial Sci Malmo, Diabetes & Cardiovasc Disease Genet Epidemi, Malmo, Sweden.
    Schupf, Nicole
    Columbia Univ, Dept Neurol, Coll Physicians & Surg, New York, NY USA;Columbia Univ, Gertrude H Sergievsky Ctr, Med Ctr, New York, NY 10027 USA;Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.
    Shaffer, Christian M.
    Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA.
    Shi, Yuan
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Smith, Albert V.
    Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp & Med Sch, Div Populat Hlth & Genom, Dundee, Scotland.
    Soranzo, Nicole
    Wellcome Sanger Inst, Human Genet, Hinxton, England.
    Spracklen, Cassandra N.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27515 USA.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany.
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Stumvoll, Michael
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Svensson, Per O.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Soder Sjukhuset, Dept Cardiol, Stockholm, Sweden.
    Szymczak, Silke
    Univ Kiel, Univ Hosp Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany.
    Tai, E-Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore;Duke NUS Med Sch, Singapore, Singapore.
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
    Tan, Nicholas Y. Q.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teren, Andrej
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Heart Ctr Leipzig, Leipzig, Germany.
    Tham, Yih-Chung
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.
    Thiery, Joachim
    Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany;Univ Leipzig, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany.
    Thio, Chris H. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Thomsen, Hauke
    German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Toniolo, Daniela
    San Raffaele Res Inst, Milan, Italy.
    Tonjes, Anke
    Univ Leipzig, Dept Endocrinol & Nephrol, Leipzig, Germany.
    Tremblay, Johanne
    CHUM, Montreal Univ Hosp, Res Ctr, Montreal, PQ, Canada;CRCHUM, Montreal, PQ, Canada.
    Tzoulaki, Ioanna
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England;Univ Ioannina, Med Sch, Dept Hyg & Epidemiol, Ioannina, Greece.
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Vaccargiu, Simona
    UOS Sassari, Natl Res Council Italy, Inst Genet & Biomed Res, Sassari, Italy.
    Van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore.
    Van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands.
    Van Duijn, Cornelia M.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Edward, Digna R. Velez
    Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA;Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth, Nashville, TN 37232 USA.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Vogelezang, Suzanne
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands;Univ Med Ctr Rotterdam, Erasmus MC, Dept Pediat, Rotterdam, Netherlands.
    Volker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Vollenweider, Peter
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Waeber, Gerard
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Waldenberger, Melanie
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wang, Ya Xing
    Capital Med Univ, Beijing Tongren Hosp, Beijing Key Lab Ophthalmol & Visual Sci, Beijing Inst Ophthalmol, Beijing, Peoples R China.
    Wang, Chaolong
    Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore;Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Wuhan, Hubei, Peoples R China.
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Bin Wei, Wen
    Capital Med Univ, Beijing Tongren Hosp, Beijing Tongren Eye Ctr, Beijing, Peoples R China.
    White, Harvey
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand;Univ Auckland, Auckland, New Zealand.
    Whitfield, John B.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
    Wild, Sarah H.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
    Wilson, James F.
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.
    Wojczynski, Mary K.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Wong, Charlene
    Natl Univ Hlth Syst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Wong, Tien-Yin
    Natl Univ Hlth Syst, Singapore, Singapore;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
    Xu, Liang
    Capital Med Univ, Beijing Tongren Hosp, Beijing Key Lab Ophthalmol & Visual Sci, Beijing Inst Ophthalmol, Beijing, Peoples R China.
    Yang, Qiong
    Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
    Yasuda, Masayuki
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore;Tohoku Univ, Grad Sch Med, Dept Ophthalmol, Sendai, Miyagi, Japan.
    Yerges-Armstrong, Laura M.
    GlaxoSmithKline, Target Sci Genet, Collegeville, PA USA.
    Zhang, Weihua
    Ealing Gen Hosp, Dept Cardiol, Middlesex, England;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US NIH, Baltimore, MD 21224 USA.
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Dept Med, Torrance, CA 90509 USA.
    Bochud, Murielle
    Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.
    Psaty, Bruce M.
    Univ Washington, Dept Hlth Serv, Dept Epidemiol, Cardiovasc Hlth Res Unit,Dept Med, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Dehghan, Abbas
    Imperial Coll London, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.
    Parsa, Afshin
    NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA;Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Ho, Kevin
    Geisinger, KHRI, Danville, PA USA;Geisinger, Dept Nephrol, Danville, PA USA.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Devuyst, Olivier
    Univ Zurich, Inst Physiol, Zurich, Switzerland.
    Akilesh, Shreeram
    Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA;Univ Washington, Med Ctr, Anat Pathol, Seattle, WA 98195 USA.
    Pendergrass, Sarah A.
    Geisinger Res, Biomed & Translat Informat Inst, Danville, PA USA.
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Boger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany;Kliniken Sudostbayern, Dept Nephrol & Rheumatol, Regensburg, Germany.
    Okada, Yukinori
    RIKEN, Ctr Integrat Med Sci IMS, Lab Stat Anal, Osaka, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan.
    Edwards, Todd L.
    Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA;Vanderbilt Univ, Med Ctr, Dept Med, Vanderbilt Genet Inst,Div Epidemiol, Nashville, TN USA.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Hung, Adriana M.
    Vanderbilt Univ, Tennessee Valley Healthcare Syst 626, Dept Vet Affairs, 221 Kirkland Hall, Nashville, TN 37235 USA;Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN USA.
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.
    Scholz, Markus
    Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany;Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Kottgen, Anna
    Univ Freiburg, Fac Med, Dept Biometry Epidemiol & Med Bioinformat, Inst Genet Epidemiol, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
    Pattaro, Cristian
    Univ Lubeck, Inst Biomed, Eurac Res, Bolzano, Italy.
    A catalog of genetic loci associated with kidney function from analyses of a million individuals2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 6, p. 957-972Article in journal (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

  • 47.
    Yi-Ting, Lin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol, Div Family Med & Primary Care, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Cardiovasc Epidemiol, Lund, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Use of Proteomics to Investigate Blood Pressure Progress in the Elderly2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, p. E115-E115Article in journal (Other academic)
1 - 47 of 47
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