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  • 1. Kilpelainen, Tuomas O.
    et al.
    Bentley, Amy R.
    Noordam, Raymond
    Sung, Yun Ju
    Schwander, Karen
    Winkler, Thomas W.
    Jakupovic, Hermina
    Chasman, Daniel I.
    Manning, Alisa
    Ntalla, Ioanna
    Aschard, Hugues
    Brown, Michael R.
    de las Fuentes, Lisa
    Franceschini, Nora
    Guo, Xiuqing
    Vojinovic, Dina
    Aslibekyan, Stella
    Feitosa, Mary F.
    Kho, Minjung
    Musani, Solomon K.
    Richard, Melissa
    Wang, Heming
    Wang, Zhe
    Bartz, Traci M.
    Bielak, Lawrence F.
    Campbell, Archie
    Dorajoo, Rajkumar
    Fisher, Virginia
    Hartwig, Fernando P.
    Horimoto, Andrea R. V. R.
    Li, Changwei
    Lohman, Kurt K.
    Marten, Jonathan
    Sim, Xueling
    Smith, Albert V.
    Tajuddin, Salman M.
    Alver, Maris
    Amini, Marzyeh
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Evangelou, Evangelos
    Gao, Chuan
    Graff, Mariaelisa
    Harris, Sarah E.
    He, Meian
    Hsu, Fang-Chi
    Jackson, Anne U.
    Zhao, Jing Hua
    Kraja, Aldi T.
    Kuehnel, Brigitte
    Laguzzi, Federica
    Lyytikainen, Leo-Pekka
    Nolte, Ilja M.
    Rauramaa, Rainer
    Riaz, Muhammad
    Robino, Antonietta
    Rueedi, Rico
    Stringham, Heather M.
    Takeuchi, Fumihiko
    van der Most, Peter J.
    Varga, Tibor V.
    Verweij, Niek
    Ware, Erin B.
    Wen, Wanqing
    Li, Xiaoyin
    Yanek, Lisa R.
    Amin, Najaf
    Arnett, Donna K.
    Boerwinkle, Eric
    Brumat, Marco
    Cade, Brian
    Canouil, Mickael
    Chen, Yii-Der Ida
    Concas, Maria Pina
    Connell, John
    de Mutsert, Renee
    de Silva, H. Janaka
    de Vries, Paul S.
    Demirkan, Ayse
    Ding, Jingzhong
    Eaton, Charles B.
    Faul, Jessica D.
    Friedlander, Yechiel
    Gabriel, Kelley P.
    Ghanbari, Mohsen
    Giulianini, Franco
    Gu, Chi Charles
    Gu, Dongfeng
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hunt, Steven C.
    Ikram, M. Arfan
    Jonas, Jost B.
    Koh, Woon-Puay
    Komulainen, Pirjo
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kutalik, Zoltan
    Kuusisto, Johanna
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Leander, Karin
    Lemaitre, Rozenn N.
    Lewis, Cora E.
    Liang, Jingjing
    Alizadeh, Behrooz Z.
    Boezen, H. Marike
    Franke, Lude
    Navis, Gerjan
    Rots, Marianne
    Swertz, Morris
    Wolffenbuttel, Bruce H. R.
    Wijmenga, Cisca
    Liu, Jianjun
    Magi, Reedik
    Manichaikul, Ani
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Mohlke, Karen L.
    Mosley, Thomas H., Jr.
    Murray, Alison D.
    Nalls, Mike A.
    Nang, Ei-Ei Khaing
    Nelson, Christopher P.
    Nona, Sotoodehnia
    Norris, Jill M.
    Nwuba, Chiamaka Vivian
    O'Connell, Jeff
    Palmer, Nicholette D.
    Papanicolau, George J.
    Pazoki, Raha
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Porteous, David J.
    Poveda, Alaitz
    Raitakari, Olli T.
    Rich, Stephen S.
    Risch, Neil
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Schreiner, Pamela J.
    Scott, Robert A.
    Sidney, Stephen S.
    Sims, Mario
    Smith, Jennifer A.
    Snieder, Harold
    Sofer, Tamar
    Starr, John M.
    Sternfeld, Barbara
    Strauch, Konstantin
    Tang, Hua
    Taylor, Kent D.
    Tsai, Michael Y.
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    van der Ende, M. Yldau
    van Heemst, Diana
    Voortman, Trudy
    Waldenberger, Melanie
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Wilson, Gregory
    Xiang, Yong-Bing
    Yao, Jie
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    de Faire, Ulf
    Deary, Ian J.
    Elliott, Paul
    Esko, Tonu
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Kato, Norihiro
    Laakso, Markku
    Lakka, Timo A.
    Lehtimaaki, Terho
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Samani, Nilesh J.
    Shu, Xiao-Ou
    van der Harst, Pim
    Van Vliet-Ostaptchouk, Jana V.
    Vollenweider, Peter
    Wagenknecht, Lynne E.
    Wang, Ya X.
    Wareham, Nicholas J.
    Weir, David R.
    Wu, Tangchun
    Zheng, Wei
    Zhu, Xiaofeng
    Evans, Michele K.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Harvard T. H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, USA; OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
    Gudnason, Vilmundur
    Hayward, Caroline
    Horta, Bernardo L.
    Kelly, Tanika N.
    Liu, Yongmei
    North, Kari E.
    Pereira, Alexandre C.
    Ridker, Paul M.
    Tai, E. Shyong
    van Dam, Rob M.
    Fox, Ervin R.
    Kardia, Sharon L. R.
    Liu, Ching-Ti
    Mook-Kanamori, Dennis O.
    Province, Michael A.
    Redline, Susan
    van Duijn, Cornelia M.
    Rotter, Jerome I.
    Kooperberg, Charles B.
    Gauderman, W. James
    Psaty, Bruce M.
    Rice, Kenneth
    Munroe, Patricia B.
    Fornage, Myriam
    Cupples, L. Adrienne
    Rotimi, Charles N.
    Morrison, Alanna C.
    Rao, Dabeeru C.
    Loos, Ruth J. F.
    Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 376Article in journal (Refereed)
    Abstract [en]

    Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

  • 2. Zheng, Ju-Sheng
    et al.
    Imamura, Fumiaki
    Sharp, Stephen J.
    van der Schouw, Yvonne T.
    Sluijs, Ivonne
    Gundersen, Thomas E.
    Ardanaz, Eva
    Boeing, Heiner
    Bonet, Catalina
    Humberto Gomez, Jesus
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Jenab, Mazda
    Kuehn, Tilman
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Lasheras, Cristina
    Mokoroa, Olatz
    Mancini, Francesca Romana
    Nilsson, Peter M.
    Overvad, Kim
    Panico, Salvatore
    Palli, Domenico
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sieri, Sabina
    Salamanca-Fernandez, Elena
    Sacerdote, Carlotta
    Spijkerman, Annemieke M. W.
    Stepien, Magdalena
    Tjonneland, Anne
    Tumino, Rosario
    Butterworth, Adam S.
    Riboli, Elio
    Danesh, John
    Langenberg, Claudia
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 4, p. 1293-1303Article in journal (Refereed)
    Abstract [en]

    Background: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D.

    Methods: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography–mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis.

    Results: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)].

    Conclusions: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.

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