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  • 1.
    Schmidt, Amand F.
    et al.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;UCLs BHF Res Accelerator Ctr, London, England.
    Holmes, Michael V.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England.
    Preiss, David
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Med Res Council Populat Hlth Res Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England.
    Swerdlow, Daniel I.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Imperial Coll London, Dept Med, London, England.
    Denaxas, Spiros
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England;British Lib, Alan Turing Inst, 96 Euston Rd, London NW1 2DB, England.
    Fatemifar, Ghazaleh
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England.
    Faraway, Rupert
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England.
    Finan, Chris
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England.
    Valentine, Dennis
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Farr Inst Hlth Informat, London, England.
    Fairhurst-Hunter, Zammy
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
    Hartwig, Fernando Pires
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil.
    Horta, Bernardo Lessa
    Univ Fed Pelotas, Postgrad Program Epidemiol, Pelotas, RS, Brazil.
    Hypponen, Elina
    Univ South Australia, Sansom Inst Hlth Res, Ctr Populat Hlth Res, Adelaide, SA, Australia;UCL GOS Inst Child Hlth, Populat Policy & Practice, London, England;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    Power, Christine
    UCL GOS Inst Child Hlth, Populat Policy & Practice, London, England.
    Moldovan, Max
    South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    van Iperen, Erik
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands;Acad Med Ctr Amsterdam, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands.
    Hovingh, Kees
    Acad Med Ctr Amsterdam, Dept Vasc Med, Amsterdam, Netherlands.
    Demuth, Ilja
    Charite Univ Med Berlin, Berlin, Germany;Free Univ Berlin, Berlin, Germany;Humboldt Univ, Berlin, Germany;Berlin Inst Hlth, Lipid Clin, Interdisciplinary Metab Ctr, Berlin, Germany;Charite Univ Med Berlin, BCRT Berlin Inst Hlth, Ctr Regenerat Therapies, Berlin, Germany.
    Norman, Kristina
    Univ Potsdam, Inst Nutr Sci, D-14558 Nuthetal, Germany;Charite Univ Med Berlin, Geriatr Res Grp, D-13347 Berlin, Germany;German Inst Human Nutr Potsdam Rehbrucke, Dept Nutr & Gerontol, D-14558 Nuthetal, Germany.
    Steinhagen-Thiessen, Elisabeth
    Charite Univ Med Berlin, Berlin, Germany;Free Univ Berlin, Berlin, Germany;Humboldt Univ, Berlin, Germany;Berlin Inst Hlth, Lipid Clin, Interdisciplinary Metab Ctr, Berlin, Germany.
    Demuth, Juri
    ECA Econ GmbH, Berlin, Germany.
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt L, Inst Neurogenet & Cardiogenet, Lubeck, Germany;Univ Oslo, Dept Psychol, Ctr Lifespan Changes Brain & Cognit LCBC, Oslo, Norway.
    Lill, Christina M.
    Univ Lubeck, Inst Neurogenet & Cardiogenet, Lubeck Interdisciplinary Platform Genome Analyt L, Genet & Mol Epidemiol Grp, Lubeck, Germany;Inst Human Genet, Lubeck, Germany;Imperial Coll, Sch Publ Hlth, Ageing Epidemiol Res Unit, London, England.
    Coassin, Stefan
    Med Univ Innsbruck, Dept Genet & Pharmacol, Inst Genet Epidemiol, A-6020 Innsbruck, Austria.
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.
    Willeit, Karin
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria;Univ Bern, Univ Hosp Bern, Inselspital, Dept Neurol, Bern, Switzerland.
    Mason, Dan
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
    Wright, John
    Bradford Royal Infirm, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
    Morris, Richard
    UCL, Dept Primary Care & Populat Hlth, London, England.
    Wanamethee, Goya
    UCL, Dept Primary Care & Populat Hlth, London, England.
    Whincup, Peter
    St Georges Univ London, Populat Hlth Res Inst, London, England.
    Ben-Shlomo, Yoav
    Univ Bristol, Populat Hlth Sci, Bristol, Avon, England.
    McLachlan, Stela
    Univ Edinburgh, Usher Inst, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
    Price, Jackie F.
    Univ Edinburgh, Usher Inst, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
    Kivimaki, Mika
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Welch, Catherine
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Sanchez-Galvez, Adelaida
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Marques-Vidal, Pedro
    Lausanne Univ Hosp, Dept Med, Internal Med, Lausanne, Switzerland.
    Nicolaides, Andrew
    Imperial Coll, Dept Vasc Surg, London, England;Univ Nicosia, Nicosia Med Sch, Dept Surg, Nicosia, Cyprus.
    Panayiotou, Andrie G.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Onland-Moret, N. Charlotte
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    van der Schouw, Yvonne T.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Matullo, Giuseppe
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Fiorito, Giovanni
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Guarrera, Simonetta
    IIGM, Turin, Italy;Univ Turin, Dept Med Sci, Turin, Italy.
    Sacerdote, Carlotta
    Citta Salute & Sci Univ Hosp, Unit Canc Epidemiol, Turin, Italy;Ctr Canc Prevent CPO, Turin, Italy.
    Wareham, Nicholas J.
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Langenberg, Claudia
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Scott, Robert A.
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Luan, Jian'an
    Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, MRC Epidemiol Unit,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
    Bobak, Martin
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Malyutina, Sofia
    Novosibirsk State Med Univ, Novosibirsk, Russia;Russian Acad Med Sci, Siberian Branch, Inst Internal & Prevent Med, Novosibirsk, Russia.
    Pajak, Andrzej
    Jagiellonian Univ, Coll Med, Fac Hlth Sci, Dept Epidemiol & Populat Studies, Krakow, Poland.
    Kubinova, Ruzena
    Natl Inst Publ Hlth, Prague, Czech Republic.
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania.
    Pikhart, Hynek
    UCL, UCL Inst Epidemiol & Hlth Care, Dept Epidemiol & Publ Hlth, London, England.
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
    Linneberg, Allan
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Capital Region, Denmark.
    Jess, Tine
    Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Copenhagen, Capital Region, Denmark.
    Cooper, Jackie
    UCL, Dept Med, Ctr Cardiovasc Genet, London, England.
    Humphries, Steve E.
    UCL, Dept Med, Ctr Cardiovasc Genet, London, England.
    Brilliant, Murray
    Marshfield Clin Res Inst, Ctr Human Genet, Marshfield, WI USA.
    Kitchner, Terrie
    Marshfield Clin Res Inst, Ctr Human Genet, Marshfield, WI USA.
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
    Carrell, David S.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    McCarty, Catherine A.
    Univ Minnesota, Minneapolis, MN USA.
    Lester, Kirchner H.
    Geisinger, Danville, PA USA.
    Larson, Eric B.
    Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Crosslin, David R.
    Univ Washington Seattle, Dept Biomed Informat & Med Educ, Seattle, WA USA.
    de Andrade, Mariza
    Mayo Clin, Rochester, MN USA.
    Roden, Dan M.
    Vanderbilt Univ, Sch Med, Dept Med, Dept Pharmacol,Dept Biomed Informat, Nashville, TN 37212 USA.
    Denny, Joshua C.
    Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
    Carty, Cara
    WHI, Seattle, WA USA.
    Hancock, Stephen
    Univ Newcastle, Newcastle, NSW, Australia.
    Attia, John
    Univ Newcastle, Newcastle, NSW, Australia;Hunter Med Res Inst, Publ Hlth Program, Newcastle, NSW, Australia.
    Holliday, Elizabeth
    Univ Newcastle, Newcastle, NSW, Australia;Hunter Med Res Inst, Publ Hlth Program, Newcastle, NSW, Australia.
    Scott, Rodney
    Univ Newcastle, Newcastle, NSW, Australia.
    Schofield, Peter
    Hunter New England Local Hlth Dist, Newcastle, NSW, Australia.
    O'Donnell, Martin
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Chong, Michael
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Pare, Guillaume
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    van der Harst, Pim
    Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands;Acad Med Ctr Amsterdam, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Eppinga, Ruben N.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
    Christen, Tim
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Mook-Kanamori, D. O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    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 epidemiology. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;.
    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.
    Pazoki, Raha
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Franco, Oscar
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Uitterlinden, Andre
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Baumeister, Sebastian
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;Ludwig Maximilians Univ Munchen, Chair Epidemiol, UNIKA T Augsburg, Augsburg, Germany.
    Doerr, Marcus
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany.
    Lerch, Markus M.
    Univ Med Greifswald, Dept Internal Med A, Greifswald, Germany.
    Voelker, Uwe
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
    Ward, Joey
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
    Pell, Jill P.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland.
    Meade, Tom
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London, England.
    Christophersen, Ingrid E.
    Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Maitland-van der Zee, Anke H.
    Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands;Univ Amsterdam, Acad Med Ctr, Dept Resp Med, Amsterdam, Netherlands.
    Baranova, Ekaterina V.
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Young, Robin
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Bots, Michiel L.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Grobbee, Diederick E.
    Cyprus Univ Technol, Cyprus Int Inst Environm & Publ Hlth, Limassol, Cyprus.
    Froguel, Philippe
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France;Imperial Coll London, Dept Genom Common Dis, London W12 0NN, England.
    Thuillier, Dorothee
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France.
    Roussel, Ronan
    INSERM, Ctr Rech Cordeliers, U1138, Paris, France;Univ Paris Diderot, Sorbonne Paris Cite, UFR Med, Paris, France;Hop Bicha, AP HP, Dept Diabetol Endocrinol & Nutr, Paris, France.
    Bonnefond, Amelie
    Univ Lille, Inst Pasteur Lille, CNRS, UMR 8199,EGID, F-59000 Lille, France.
    Cariou, Bertrand
    Univ Nantes, CHU Nantes, CNRS, Inst Thorax,INSERM, Nantes, France.
    Smart, Melissa
    Univ Essex, Inst Social & Econ Res, Colchester, Essex, England.
    Bao, Yanchun
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Kumari, Meena
    Boston Univ, Sch Med, Boston, MA 02118 USA.
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.
    Seshadri, Sudha
    Boston Univ, Sch Med, Boston, MA 02118 USA.
    Dale, Caroline
    UCL, Farr Inst Hlth Informat, London, England.
    Costa, Rui Providencia E.
    UCL, Farr Inst Hlth Informat, London, England.
    Ridker, Paul M.
    Harvard Med Sch, Ctr Cardiovasc Dis Prevent, Brigham & Womens Hosp, Boston, MA 02115 USA.
    Chasman, Daniel I.
    Harvard Med Sch, Ctr Cardiovasc Dis Prevent, Brigham & Womens Hosp, Boston, MA 02115 USA.
    Reiner, Alex P.
    UWash, Seattle, WA USA.
    Ritchie, Marylyn D.
    Penn State, State Coll, PA USA.
    Lange, Leslie A.
    Univ Colorado Denver, Denver, CO USA.
    Cornish, Alex J.
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Dobbins, Sara E.
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Hemminki, Kari
    German Canc Res Ctr, Div Mol Genet Epidemiol, Neuenheimer Feld 580, D-69120 Heidelberg, Germany;Deutsch Krebsforschungszentrum, Heidelberg, Germany.
    Kinnersley, Ben
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Sanson, Marc
    Inst Cerveau Moelle Epiniere ICM, Paris, France;UPMC Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France.
    Labreche, Karim
    Inst Cerveau Moelle Epiniere ICM, Paris, France;UPMC Univ Paris 06, Sorbonne Univ, UMR S 1127, F-75013 Paris, France.
    Simon, Matthias
    Bethel Clin, Dept Neurosurg, Kantensiek 11, D-33617 Bielefeld, Germany.
    Bondy, Melissa
    Baylor Coll Med, Dan L Duncan Canc Ctr, Dept Pediat, Div Hematol Oncol, Houston, TX 77030 USA.
    Law, Philip
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Speedy, Helen
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Allan, James
    Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England.
    Li, Ni
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Went, Molly
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Weinhold, Niels
    Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
    Morgan, Gareth
    Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
    Sonneveld, Pieter
    Erasmus MC Canc Inst, Dept Hematol, NL-3075 EA Rotterdam, Netherlands.
    Nilsson, Bjorn
    Dept Lab Med, Hematol & Transfus Med, BMC B13, SE-22184 Lund, Sweden.
    Goldschmidt, Hartmut
    Univ Clin Heidelberg, Internal Med 5, Heidelberg, Germany;Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
    Sud, Amit
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Engert, Andreas
    Univ Hosp Cologne, Dept Internal Med, Cologne, Germany.
    Hansson, Markus
    Skane Univ Hosp, Hematol Clin, Skane, Sweden;Lund Univ, Wallenberg Ctr Mol Med, Lund, Sweden.
    Hemingway, Harry
    UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, 222 Euston Rd, London NW1 2DA, England;UCL, Inst Hlth Informat, 222 Euston Rd, London NW1 2DA, England;UCL, Univ Coll London Hosp, Biomed Res Ctr, Natl Inst Hlth Res, 222 Euston Rd, London NW1 2DA, England.
    Asselbergs, Folkert W.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands;UCLs BHF Res Accelerator Ctr, London, England;UCL, Hlth Data Res UK, London, England;UCL, Inst Hlth Informat, London, England.
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England;St Bartholomews Hosp, Barts Heart Ctr, London, England.
    Keating, Brendan J.
    Univ Penn, Philadelphia, PA 19104 USA.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland.
    Houlston, Richard
    Inst Canc Res, Div Genet & Epidemiol, London, England.
    Casas, Juan P.
    Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA.
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, 222 Euston Rd, London NW1 2DA, England;UCLs BHF Res Accelerator Ctr, London, England.
    Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK92019In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 19, no 1, article id 240Article in journal (Refereed)
    Abstract [en]

    Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

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