The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg B Ehret^#^{1

2}, Teresa Ferreira^#³, Daniel I Chasman^{4

5}, Anne U Jackson^{6

7}, Ellen M Schmidt⁸, Toby Johnson^{9

10}, Gudmar Thorleifsson¹¹, Jian'an Luan¹², Lousie A Donnelly¹³, Stavroula Kanoni¹⁴, Ann-Kristin Petersen¹⁵, Vasyl Pihur¹, Rona J Strawbridge^{16

17}, Dmitry Shungin^{18

19

20}, Maria F Hughes²¹, Osorio Meirelles²², Marika Kaakinen²³, Nabila Bouatia-Naji^{24

25}, Kati Kristiansson^{26

27}, Sonia Shah²⁸, Marcus E Kleber²⁹, Xiuqing Guo³⁰, Leo-Pekka Lyytikäinen^{31

32}, Cristiano Fava^{33

34}, Niclas Eriksson³⁵, Ilja M Nolte³⁶, Patrik K Magnusson³⁷, Elias L Salfati³⁸, Loukianos S Rallidis³⁹, Elizabeth Theusch⁴⁰, Andrew J P Smith⁴¹, Lasse Folkersen¹⁶, Kate Witkowska^{9

42}, Tune H Pers^{43

44

45

46

47}, Roby Joehanes⁴⁸, Stuart K Kim⁴⁹, Lazaros Lataniotis¹⁴, Rick Jansen⁵⁰, Andrew D Johnson^{48

51}, Helen Warren^{9

42}, Young Jin Kim⁵², Wei Zhao⁵³, Ying Wu⁵⁴, Bamidele O Tayo⁵⁵, Murielle Bochud⁵⁶; CHARGE-EchoGen consortium; CHARGE-HF consortium; Wellcome Trust Case Control Consortium; Devin Absher⁵⁷, Linda S Adair⁵⁸, Najaf Amin⁵⁹, Dan E Arking¹, Tomas Axelsson⁶⁰, Damiano Baldassarre^{61

62}, Beverley Balkau⁶³, Stefania Bandinelli⁶⁴, Michael R Barnes^{14

42}, Inês Barroso^{65

66

67}, Stephen Bevan⁶⁸, Joshua C Bis⁶⁹, Gyda Bjornsdottir¹¹, Michael Boehnke^{6

7}, Eric Boerwinkle⁷⁰, Lori L Bonnycastle⁷¹, Dorret I Boomsma⁷², Stefan R Bornstein⁷³, Morris J Brown⁷⁴, Michel Burnier⁷⁵, Claudia P Cabrera^{9

42}, John C Chambers^{76

77

78}, I-Shou Chang⁷⁹, Ching-Yu Cheng^{80

81

82}, Peter S Chines⁷¹, Ren-Hua Chung⁸³, Francis S Collins⁷¹, John M Connell⁸⁴, Angela Döring^{85

86}, Jean Dallongeville⁸⁷, John Danesh^{88

65

89}, Ulf de Faire⁹⁰, Graciela Delgado²⁹, Anna F Dominiczak⁹¹, Alex S F Doney¹³, Fotios Drenos⁴¹, Sarah Edkins⁶⁵, John D Eicher^{48

51}, Roberto Elosua⁹², Stefan Enroth^{93

94}, Jeanette Erdmann^{95

96}, Per Eriksson¹⁶, Tonu Esko^{97

98

99}, Evangelos Evangelou^{76

100}, Alun Evans²¹, Tove Fall¹⁰¹, Martin Farrall^{3

102}, Janine F Felix¹⁰³, Jean Ferrières¹⁰⁴, Luigi Ferrucci¹⁰⁵, Myriam Fornage¹⁰⁶, Terrence Forrester¹⁰⁷, Nora Franceschini¹⁰⁸, Oscar H Franco Duran¹⁰³, Anders Franco-Cereceda¹⁰⁰, Ross M Fraser^{109

110}, Santhi K Ganesh¹¹¹, He Gao⁷⁶, Karl Gertow^{16

17}, Francesco Gianfagna^{112

113}, Bruna Gigante⁹⁰, Franco Giulianini⁴, Anuj Goel^{3

102}, Alison H Goodall^{114

115}, Mark O Goodarzi¹¹⁶, Mathias Gorski^{117

118}, Jürgen Gräßler¹¹⁹, Christopher Groves¹²⁰, Vilmundur Gudnason^{121

122}, Ulf Gyllensten^{93

94}, Göran Hallmans¹⁸, Anna-Liisa Hartikainen^{123

124}, Maija Hassinen¹²⁵, Aki S Havulinna²⁶, Caroline Hayward¹²⁶, Serge Hercberg¹²⁷, Karl-Heinz Herzig^{128

129

130}, Andrew A Hicks¹³¹, Aroon D Hingorani²⁸, Joel N Hirschhorn^{43

44

45

132}, Albert Hofman^{103

133}, Jostein Holmen¹³⁴, Oddgeir Lingaas Holmen^{134

135}, Jouke-Jan Hottenga⁷², Phil Howard⁴¹, Chao A Hsiung⁸³, Steven C Hunt^{136

137}, M Arfan Ikram^{103

138

139}, Thomas Illig^{140

141

142}, Carlos Iribarren¹⁴³, Richard A Jensen^{70

144}, Mika Kähönen¹⁴⁵, Hyun Kang^{6

7}, Sekar Kathiresan^{146

147

148

45

149}, Brendan J Keating^{150

151}, Kay-Tee Khaw¹⁵², Yun Kyoung Kim⁵², Eric Kim¹⁵³, Mika Kivimaki²⁸, Norman Klopp^{140

141}, Genovefa Kolovou¹⁵⁴, Pirjo Komulainen¹²⁵, Jaspal S Kooner^{155

77

78}, Gulum Kosova^{147

146

99}, Ronald M Krauss¹⁵⁶, Diana Kuh¹⁵⁷, Zoltan Kutalik^{158

159}, Johanna Kuusisto¹⁶⁰, Kirsti Kvaløy¹³⁴, Timo A Lakka^{161

125

162}, Nanette R Lee^{163

164}, I-Te Lee^{165

166}, Wen-Jane Lee¹⁶⁷, Daniel Levy^{48

168}, Xiaohui Li³⁰, Kae-Woei Liang^{169

170}, Honghuang Lin^{171

48}, Li Lin², Jaana Lindström²⁶, Stéphane Lobbens^{172

173

174}, Satu Männistö²⁶, Gabriele Müller¹⁷⁵, Martina Müller-Nurasyid^{15

176

177}, François Mach², Hugh S Markus¹⁷⁸, Eirini Marouli^{14

179}, Mark I McCarthy¹²⁰, Colin A McKenzie¹⁰⁷, Pierre Meneton¹⁸⁰, Cristina Menni¹⁸¹, Andres Metspalu⁹⁷, Vladan Mijatovic¹⁸², Leena Moilanen^{183

184}, May E Montasser¹⁸⁵, Andrew D Morris¹³, Alanna C Morrison¹⁸⁶, Antonella Mulas¹⁸⁷, Ramaiah Nagaraja²², Narisu Narisu⁷¹, Kjell Nikus^{188

189}, Christopher J O'Donnell^{190

48

149}, Paul F O'Reilly¹⁹¹, Ken K Ong¹², Fred Paccaud⁵⁶, Cameron D Palmer^{192

193

45}, Afshin Parsa¹⁸⁵, Nancy L Pedersen³⁷, Brenda W Penninx^{194

195

196}, Markus Perola^{26

27

97}, Annette Peters⁸⁶, Neil Poulter¹⁹⁷, Peter P Pramstaller^{131

198

199}, Bruce M Psaty^{69

200

201

202}, Thomas Quertermous³⁸, Dabeeru C Rao²⁰³, Asif Rasheed²⁰⁴, N William N W R Rayner^{120

3

65}, Frida Renström^{19

205

18}, Rainer Rettig²⁰⁶, Kenneth M Rice²⁰⁷, Robert Roberts^{208

209}, Lynda M Rose⁴, Jacques Rossouw²¹⁰, Nilesh J Samani^{114

211}, Serena Sanna¹⁸⁷, Jouko Saramies²¹², Heribert Schunkert^{213

214

215

216}, Sylvain Sebert^{217

129

162}, Wayne H-H Sheu^{165

166

218}, Young-Ah Shin⁵², Xueling Sim^{6

7

219}, Johannes H Smit¹⁹⁴, Albert V Smith^{121

122}, Maria X Sosa¹, Tim D Spector¹⁸¹, Alena Stančáková²²⁰, Alice Stanton²²¹, Kathleen E Stirrups^{14

222}, Heather M Stringham^{6

7}, Johan Sundstrom⁶⁰, Amy J Swift⁷¹, Ann-Christine Syvänen⁶⁰, E-Shyong Tai^{223

81

219}, Toshiko Tanaka¹⁰⁵, Kirill V Tarasov²²⁴, Alexander Teumer²²⁵, Unnur Thorsteinsdottir^{11

122}, Martin D Tobin²²⁶, Elena Tremoli^{61

62}, Andre G Uitterlinden^{103

227}, Matti Uusitupa^{228

229}, Ahmad Vaez^{36

230}, Dhananjay Vaidya²³¹, Cornelia M van Duijn^{103

232}, Erik P A van Iperen^{233

234}, Ramachandran S Vasan^{48

235

236}, Germaine C Verwoert¹⁰³, Jarmo Virtamo²⁶, Veronique Vitart¹²⁶, Benjamin F Voight^{45

237}, Peter Vollenweider²³⁸, Aline Wagner²³⁹, Louise V Wain²²⁶, Nicholas J Wareham¹², Hugh Watkins^{3

102}, Alan B Weder²⁴⁰, Harm-Jan Westra²⁴¹, Rainford Wilks²⁴², Tom Wilsgaard^{243

244}, James F Wilson^{109

126}, Tien Y Wong^{80

81

82}, Tsun-Po Yang^{14

245}, Jie Yao³⁰, Loic Yengo^{172

173

174}, Weihua Zhang^{76

77}, Jing Hua Zhao¹², Xiaofeng Zhu²⁴⁶, Pascal Bovet^{247

56}, Richard S Cooper⁵⁵, Karen L Mohlke⁵⁴, Danish Saleheen^{248

204}, Jong-Young Lee⁵², Paul Elliott^{76

249}, Hinco J Gierman^{49

250}, Cristen J Willer^{8

251

252}, Lude Franke²⁵³, G Kees Hovingh²⁵⁴, Kent D Taylor³⁰, George Dedoussis¹⁷⁹, Peter Sever¹⁹⁷, Andrew Wong¹⁵⁷, Lars Lind⁶⁰, Themistocles L Assimes³⁸, Inger Njølstad^{243

244}, Peter Eh Schwarz⁷³, Claudia Langenberg¹², Harold Snieder³⁶, Mark J Caulfield^{9

42}, Olle Melander³³, Markku Laakso¹⁶⁰, Juha Saltevo²⁵⁵, Rainer Rauramaa^{125

162}, Jaakko Tuomilehto^{26

256

257

258}, Erik Ingelsson^{101

3}, Terho Lehtimäki^{31

32}, Kristian Hveem¹³⁴, Walter Palmas²⁵⁹, Winfried März^{260

261}, Meena Kumari²⁸, Veikko Salomaa²⁶, Yii-Der I Chen³⁰, Jerome I Rotter³⁰, Philippe Froguel^{172

173

174

23}, Marjo-Riitta Jarvelin^{217

129

262

249}, Edward G Lakatta²²⁴, Kari Kuulasmaa²⁶, Paul W Franks^{19

205

18}, Anders Hamsten^{16

17}, H-Erich Wichmann^{85

177

263}, Colin N A Palmer¹³, Kari Stefansson^{11

122}, Paul M Ridker^{4

5}, Ruth J F Loos^{12

264

265}, Aravinda Chakravarti¹, Panos Deloukas^{14

266}, Andrew P Morris^{267

3}, Christopher Newton-Cheh^{146

147

45

99}, Patricia B Munroe^{9

42}

Affiliations

¹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Cardiology, Department of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
³ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁴ Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. East, Boston, MA 02215, USA.
⁵ Harvard Medical School, Boston, MA 02115, USA.
⁶ Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
⁷ Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
⁸ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
⁹ Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
¹⁰ GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
¹¹ deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
¹² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
¹³ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
¹⁴ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
¹⁵ Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
¹⁶ Cardiovascular Research Unit, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
¹⁷ Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
¹⁸ Department of Public Health and Clinical Medicine, Umeå University, Sweden.
¹⁹ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, SE-205 02 Malmö, Sweden.
²⁰ Department of Odontology, Umeå University, Sweden.
²¹ Centre of Excellence for Public Health, Queens University Belfast, Grosvenor Road, Belfast BT126JP, UK.
²² Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
²³ Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
²⁴ INSERM UMR970, Paris Cardiovascular Research Center PARCC, 56 rue Leblanc, 75015 Paris, France.
²⁵ University Paris-Descartes, Sorbonne Paris Cité, 12 rue de l'Ecole de medicine, F-75006 Paris, France.
²⁶ National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
²⁷ Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00290 Helsinki, Finland.
²⁸ Genetic Epidemiology Group, Dept. Epidemiology and Public Health, UCL, London, WC1E 6BT, UK.
²⁹ Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
³⁰ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, USA.
³¹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.
³² Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
³³ University of Lund, Dept Internal Medicine, Malmo, SE 20502, Sweden.
³⁴ University of Verona, Dept of Internal Medicine, Verona, Italy 37134.
³⁵ Uppsala University, Uppsala Clinical Research Center, SE-75185 Uppsala, Sweden.
³⁶ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
³⁷ Dept of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden.
³⁸ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
³⁹ Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.
⁴⁰ Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
⁴¹ Department of Cardiovascular Genetics, Institute of Cardiovascular Sciences, University College London, London WC1E 6JF, UK.
⁴² NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, EC1M 6BQ, UK.
⁴³ Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
⁴⁴ Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
⁴⁵ Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
⁴⁶ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic, Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
⁴⁷ Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen, Denmark.
⁴⁸ National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
⁴⁹ Dept. Dev. Bio. And Genetics, Stanford University Medical Center, Stanford, CA 94305, USA.
⁵⁰ Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
⁵¹ National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, MD 20814, USA.
⁵² Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
⁵³ Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennyslvania, USA.
⁵⁴ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵⁵ Department of Preventive Medicine and Epidemiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 60153, USA.
⁵⁶ Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Route de la Corniche 10, 1010 Lausanne, Switzerland.
⁵⁷ HudsonAlpha Institute for Biotechnology, Huntsville, AL 35086, USA.
⁵⁸ Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵⁹ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, 3015CN, The Netherlands.
⁶⁰ Uppsala University, Department of Medical Sciences, SE-75185 Uppsala, Sweden.
⁶¹ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.
⁶² Centro Cardiologico Monzino, IRCCS, Milan, Italy.
⁶³ INSERM Centre for Research in Epidemiology and Population Health, U1018, Villejuif, France University Paris-Sud, URMS 1018, Villejuif, France.
⁶⁴ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
⁶⁵ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, UK.
⁶⁶ University of Cambridge Metabolic Research Laboratories, Level 4, Institute of Metabolic Science Box 289 Addenbrookes Hospital Cambridge CB2 OQQ, UK.
⁶⁷ NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrookes Hospital Cambridge CB2 OQQ, UK.
⁶⁸ School of Life Science, University of Lincoln, Joseph Banks Laboratories, Lincoln LN6 7DL, UK.
⁶⁹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
⁷⁰ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler St., Suite 453E, Houston, TX 77030, USA.
⁷¹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷² Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
⁷³ Dept of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
⁷⁴ The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
⁷⁵ Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 17, 1005 Lausanne, Switzerland.
⁷⁶ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
⁷⁷ Department of Cardiology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex UB1 3EU, UK.
⁷⁸ Imperial College Healthcare NHS Trust, London, UK.
⁷⁹ National Institute of Cancer Research, National Health Research Institutes. 35 Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
⁸⁰ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
⁸¹ Duke-NUS Graduate Medical School Singapore, Singapore 169857, Singapore.
⁸² Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228.
⁸³ Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes. 35 Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
⁸⁴ University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
⁸⁵ Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁶ Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁷ UMR744 Inserm-Lille2-Institut Pasteur Lille, France.
⁸⁸ Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁸⁹ NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁹⁰ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁹¹ BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8QT, UK.
⁹² Cardiovascular Epidemiology and Genetics. IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
⁹³ Department of Immunology, Genetics and Pathology, University of Uppsala, Box 815, Biomerical center, 751 08 Uppsala, Sweden.
⁹⁴ Science for Life Laboratory, University of Uppsala, Box 815, Biomerical center, 751 08 Uppsala, Sweden.
⁹⁵ Institut für Integrative und Experimentelle Genomik, Universiät zu Lübeck, RatzeburgerAllee 160, 23538 Lübeck, Germany.
⁹⁶ Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Hamburg, Kiel, Lübeck, Universität zu Lübeck, Lübeck, Germany.
⁹⁷ Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
⁹⁸ Divisions of Endocrinology/Children's Hospital, Boston, MA 02115, USA.
⁹⁹ Broad Institute of Harvard and MIT, Cambridge, MA 02139 USA.
¹⁰⁰ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
¹⁰¹ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁰² Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
¹⁰³ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands.
¹⁰⁴ Toulouse University School of Medicine, Rangueil University Hospital, INSERM UMR1027, Toulouse, France.
¹⁰⁵ Translational Gerontology Branch, National Institute on Aging, Baltimore MD, USA.
¹⁰⁶ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, TX, USA.
¹⁰⁷ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
¹⁰⁸ Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
¹⁰⁹ Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
¹¹⁰ Synpromics Ltd, 9 Bioquarter, Little France Road, Edinburgh, EH16 4UX, Scotland.
¹¹¹ University of Michigan Medical School, 7220 MSRB III, Ann Arbor MI 48109, USA.
¹¹² EPIMED Research Centre - Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
¹¹³ Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, Italy.
¹¹⁴ Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
¹¹⁵ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
¹¹⁶ Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹¹⁷ Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
¹¹⁸ Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
¹¹⁹ Department of Medicine III, Division Pathobiochemistry, Technische Universität Dresden, Dresden, Germany.
¹²⁰ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
¹²¹ Icelandic Heart Association, Kopavogur, Iceland.
¹²² Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹²³ Institute of Clinical Medicine/Obstetrics and Gynaecology, University of Oulu, Oulu, Finland.
¹²⁴ Medical Research Center, Oulu University Hospital, Oulu, Finland.
¹²⁵ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
¹²⁶ Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU Scotland, UK.
¹²⁷ UREN, INSERM U557, INRA U1125, CNAM, SMBH, Sorbonne Paris Cité, Université Paris 13, Bobigny, France.
¹²⁸ Institute of Biomedicine, University of Oulu, Medical Research Center Oulu and Oulu University Hospital, Finland.
¹²⁹ Biocenter Oulu, P.O.Box 5000, Aapistie 5A, FI-90014 University of Oulu, Finland.
¹³⁰ Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
¹³¹ Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, 39100, Italy - affiliated institute of the University of Lübeck, Germany.
¹³² Department of Genetics, Harvard Medical School, Boston, 02115, USA.
¹³³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹³⁴ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway.
¹³⁵ St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.
¹³⁶ Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹³⁷ Department of Genetic Medicine, Weill Cornell Medical College Qatar, Doha, Qatar.
¹³⁸ Department of Radiology, Erasmus MC, The Netherlands.
¹³⁹ Department of Neurology, Erasmus MC, University Medical Center Rotterdam, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands.
¹⁴⁰ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
¹⁴¹ Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany.
¹⁴² Hannover Medical School, Institute for Human Genetics, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
¹⁴³ Kaiser Permanente, Division of Research, Oakland, CA 94612, USA.
¹⁴⁴ Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
¹⁴⁵ Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland.
¹⁴⁶ Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁴⁷ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁴⁸ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁴⁹ Cardiology Division, Department of Medicine, Massachusetts General Hospital.
¹⁵⁰ Division of Transplantation, Department of Surgery, University of Pennsylvania, PA 19104 USA.
¹⁵¹ Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA.
¹⁵² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK.
¹⁵³ Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, USA.
¹⁵⁴ 1st Cardiology Department, Onassis Cardiac Surgery Center 356, Sygrou Ave, Athens, Greece.
¹⁵⁵ National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, Ducane Road, London W12 0NN, UK.
¹⁵⁶ Department of Medicine, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
¹⁵⁷ MRC Unit for Lifelong Health and Ageing at UCL, London, WC1B 5JU, UK.
¹⁵⁸ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
¹⁵⁹ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹⁶⁰ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹⁶¹ Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland.
¹⁶² Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁶³ Office of Population Studies Foundation Inc., Talamban, Cebu City, 6000, Philippines.
¹⁶⁴ Department of Anthropology, Sociology, and History, University of San Carlos, Talamban, Cebu City, 6000, Philippines.
¹⁶⁵ Division of Endocrine and Metabolism, Department of Internal Medicine, Chichung Veterans General Hospital, Taichung 40705, Taiwan.
¹⁶⁶ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁶⁷ Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
¹⁶⁸ Population Sciences Branch, National Heart Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁶⁹ Cardiovascular Center, Taichung Veterans General Hospital, Taichung, 40705, Taiwan.
¹⁷⁰ Institute of Clinical Medicine, National Yang Ming University School of Medicine, Taipei 112, Taiwan.
¹⁷¹ Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
¹⁷² European Genomic Institute for Diabetes (EGID), FR 3508 Lille, France.
¹⁷³ Centre National de la Recherche Scientifique (CNRS) UMR 8199, Lille Pasteur Institute, 1 rue du Prof Calmette, 59019 Lille Cedex, France.
¹⁷⁴ Lille 2 University, Lille, France.
¹⁷⁵ Center for Evidence-based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁷⁶ Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany.
¹⁷⁷ Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, München 81377, Germany.
¹⁷⁸ Neurology Unit, University of Cambridge, R3, Box 83, Cambridge Biomedical Campus, Cambridge, Cb2 0QQ, UK.
¹⁷⁹ Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
¹⁸⁰ INSERM U1142 LIMICS, UMR_S 1142 Sorbonne Universités, UPMC Université Paris 06, Université Paris 13, Paris, France.
¹⁸¹ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹⁸² Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie 8, 37134 Verona, Italy.
¹⁸³ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁸⁴ Unit of General Practice, Oulu University Hospital, Oulu, Finland.
¹⁸⁵ Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
¹⁸⁶ Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler St., Suite 453E, Houston, TX 77030, USA.
¹⁸⁷ Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monseratto, Monserrato, Cagliari 09042, Italy.
¹⁸⁸ Department of Cardiology, School of Medicine, University of Tampere, Tampere 33014, Finland.
¹⁸⁹ School of Medicine, University of Tampere, Tampere 33014, Finland.
¹⁹⁰ National Heart, Lung and Blood Institute, Division of Intramural Research, Bethesda, MD, USA.
¹⁹¹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
¹⁹² Divisions of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA.
¹⁹³ Genetics and Program in Genomics, Children's Hospital Boston, Massachusetts 02115, USA.
¹⁹⁴ Department of Psychiatry, EMGO Institute, Neuroscience Campus, VU University Medical Centre, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
¹⁹⁵ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
¹⁹⁶ Department of Psychiatry, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
¹⁹⁷ International Centre for Circulatory Health, Imperial College London, W2 1PG, UK.
¹⁹⁸ Department of Neurology, General Central Hospital, Bolzano, 39100, Italy.
¹⁹⁹ Department of Neurology, University of Lübeck, Lübeck, Germany.
²⁰⁰ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²⁰¹ Department of Health Services, University of Washington, Seattle, WA.
²⁰² Group Health Research Institute, Group Health Cooperative, Seattle, WA.
²⁰³ Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
²⁰⁴ Center for Non-Communicable Diseases, Karachi, Pakistan.
²⁰⁵ Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
²⁰⁶ Institute of Physiology, University Medicine Greifswald, Greifswald, Germany.
²⁰⁷ Department of Biostatistics, University of Washington, Seattle, WA, USA.
²⁰⁸ University of Ottawa Heart Institute, Cardiovascular Research Methods Centre Ontario, Canada.
²⁰⁹ Ruddy Canadian Cardiovascular Genetics Centre, Ontario, Canada.
²¹⁰ National Heart, Lung, and Blood Institute, 6701 Rockledge Ave., Bethesda, MD 20892, USA.
²¹¹ Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK.
²¹² South Karelia Central Hospital, Lappeenranta, Finland.
²¹³ Deutsches Herzzentrum München, Germany.
²¹⁴ Technische Universität München, Germany.
²¹⁵ Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), München, Germany.
²¹⁶ Munich Heart Alliance, Germany.
²¹⁷ Center For Life-course Health Research, P.O.Box 5000, FI-90014 University of Oulu, Finland.
²¹⁸ College of Medicine, National Defense Medical Center, Taipei, Taiwan.
²¹⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597.
²²⁰ University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
²²¹ Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
²²² Department of Haematology, University of Cambridge, Cambridge, UK.
²²³ Department of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
²²⁴ Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 21224, USA.
²²⁵ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
²²⁶ Department of Health Sciences, University of Leicester, University Rd, Leicester LE1 7RH, UK.
²²⁷ Department of internal medicine, Erasmus MC, Rotterdam, 3000CA, The Netherlands.
²²⁸ Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
²²⁹ Research Unit, Kuopio University Hospital, Kuopio, Finland.
²³⁰ Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
²³¹ Johns Hopkins Medical Institutions, 1830 East Monument St., Baltimore, MD 21287, USA.
²³² Centre of Medical Systems Biology (CMSB 1-2), NGI Erasmus Medical Center, Rotterdam, The Netherlands.
²³³ Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
²³⁴ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
²³⁵ Section of Preventive medicine, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
²³⁶ Cardiology, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
²³⁷ Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²³⁸ Department of Internal medicine, University Hospital Lausanne, Lausanne, Switzerland.
²³⁹ Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Strasbourg, France.
²⁴⁰ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
²⁴¹ University Medical Center Groningen, University of Groningen, Groningen, 9700RB, The Netherlands.
²⁴² Epidemiology Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
²⁴³ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
²⁴⁴ Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
²⁴⁵ MRC Cancer Unit, University of Cambridge, Cambridge, UK.
²⁴⁶ Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
²⁴⁷ Ministry of Health, Victoria, Republic of Seychelles.
²⁴⁸ Department of Biostatistics and Epidemiology, University of Pennsylvania, USA.
²⁴⁹ MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
²⁵⁰ Enterprise Informatics, Illumina Inc., Santa Clara CA, 95050, USA.
²⁵¹ Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
²⁵² Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
²⁵³ Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, 9711, The Netherlands.
²⁵⁴ Dept Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
²⁵⁵ Department of Medicine, Central Finland Health Care District, Jyväskylä, Finland.
²⁵⁶ Dasman Diabetes Institute, Dasman, 15462 Kuwait.
²⁵⁷ Saudi Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
²⁵⁸ Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
²⁵⁹ Department of Medicine, Columbia University, 622 West 168th St., New York, NY 10032, USA.
²⁶⁰ Synlab Academy, Synlab Services GmbH, P5, 7, 68161 Mannheim, Germany.
²⁶¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.
²⁶² Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O.Box 20, FI-90220 Oulu, 90029 OYS, Finland.
²⁶³ Grosshadern, Klinikum, München 81377, Germany.
²⁶⁴ The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁶⁵ Mindich Child health Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁶⁶ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
²⁶⁷ Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK.

^# Contributed equally.

PMID: 27618452
PMCID: PMC5042863
DOI: 10.1038/ng.3667

Meta-Analysis

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg B Ehret et al. Nat Genet. 2016 Oct.

. 2016 Oct;48(10):1171-1184.

doi: 10.1038/ng.3667. Epub 2016 Sep 12.

Authors

Affiliations

¹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Cardiology, Department of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland.
³ Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.
⁴ Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. East, Boston, MA 02215, USA.
⁵ Harvard Medical School, Boston, MA 02115, USA.
⁶ Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
⁷ Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
⁸ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
⁹ Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK.
¹⁰ GlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK.
¹¹ deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
¹² MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
¹³ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
¹⁴ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
¹⁵ Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
¹⁶ Cardiovascular Research Unit, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
¹⁷ Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
¹⁸ Department of Public Health and Clinical Medicine, Umeå University, Sweden.
¹⁹ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, SE-205 02 Malmö, Sweden.
²⁰ Department of Odontology, Umeå University, Sweden.
²¹ Centre of Excellence for Public Health, Queens University Belfast, Grosvenor Road, Belfast BT126JP, UK.
²² Laboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
²³ Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
²⁴ INSERM UMR970, Paris Cardiovascular Research Center PARCC, 56 rue Leblanc, 75015 Paris, France.
²⁵ University Paris-Descartes, Sorbonne Paris Cité, 12 rue de l'Ecole de medicine, F-75006 Paris, France.
²⁶ National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
²⁷ Institute for Molecular Medicine Finland FIMM, University of Helsinki, 00290 Helsinki, Finland.
²⁸ Genetic Epidemiology Group, Dept. Epidemiology and Public Health, UCL, London, WC1E 6BT, UK.
²⁹ Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
³⁰ Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, USA.
³¹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland.
³² Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland.
³³ University of Lund, Dept Internal Medicine, Malmo, SE 20502, Sweden.
³⁴ University of Verona, Dept of Internal Medicine, Verona, Italy 37134.
³⁵ Uppsala University, Uppsala Clinical Research Center, SE-75185 Uppsala, Sweden.
³⁶ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
³⁷ Dept of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden.
³⁸ Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
³⁹ Second Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece.
⁴⁰ Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
⁴¹ Department of Cardiovascular Genetics, Institute of Cardiovascular Sciences, University College London, London WC1E 6JF, UK.
⁴² NIHR Barts Cardiovascular Biomedical Research Unit, Queen Mary University of London, London, EC1M 6BQ, UK.
⁴³ Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
⁴⁴ Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, MA 02115, USA.
⁴⁵ Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
⁴⁶ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic, Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
⁴⁷ Department of Epidemiology Research, Statens Serum Institut, 2300, Copenhagen, Denmark.
⁴⁸ National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
⁴⁹ Dept. Dev. Bio. And Genetics, Stanford University Medical Center, Stanford, CA 94305, USA.
⁵⁰ Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
⁵¹ National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, MD 20814, USA.
⁵² Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
⁵³ Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennyslvania, USA.
⁵⁴ Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵⁵ Department of Preventive Medicine and Epidemiology, Loyola University Chicago Stritch School of Medicine, Maywood, IL, 60153, USA.
⁵⁶ Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Route de la Corniche 10, 1010 Lausanne, Switzerland.
⁵⁷ HudsonAlpha Institute for Biotechnology, Huntsville, AL 35086, USA.
⁵⁸ Department of Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA.
⁵⁹ Genetic Epidemiology Unit, Department of Epidemiology, Erasmus MC, Rotterdam, 3015CN, The Netherlands.
⁶⁰ Uppsala University, Department of Medical Sciences, SE-75185 Uppsala, Sweden.
⁶¹ Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan, Italy.
⁶² Centro Cardiologico Monzino, IRCCS, Milan, Italy.
⁶³ INSERM Centre for Research in Epidemiology and Population Health, U1018, Villejuif, France University Paris-Sud, URMS 1018, Villejuif, France.
⁶⁴ Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy.
⁶⁵ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, UK.
⁶⁶ University of Cambridge Metabolic Research Laboratories, Level 4, Institute of Metabolic Science Box 289 Addenbrookes Hospital Cambridge CB2 OQQ, UK.
⁶⁷ NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrookes Hospital Cambridge CB2 OQQ, UK.
⁶⁸ School of Life Science, University of Lincoln, Joseph Banks Laboratories, Lincoln LN6 7DL, UK.
⁶⁹ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
⁷⁰ Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler St., Suite 453E, Houston, TX 77030, USA.
⁷¹ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
⁷² Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
⁷³ Dept of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
⁷⁴ The Barts Heart Centre, William Harvey Research Institute, Queen Mary University of London, London EC1M 6BQ, UK.
⁷⁵ Nephrology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 17, 1005 Lausanne, Switzerland.
⁷⁶ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
⁷⁷ Department of Cardiology, Ealing Hospital NHS Trust, Uxbridge Road, Southall, Middlesex UB1 3EU, UK.
⁷⁸ Imperial College Healthcare NHS Trust, London, UK.
⁷⁹ National Institute of Cancer Research, National Health Research Institutes. 35 Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
⁸⁰ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751, Singapore.
⁸¹ Duke-NUS Graduate Medical School Singapore, Singapore 169857, Singapore.
⁸² Department of Ophthalmology, National University of Singapore and National University Health System, Singapore 119228.
⁸³ Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes. 35 Keyan Rd., Zhunan Town, Miaoli County 350, Taiwan.
⁸⁴ University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.
⁸⁵ Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁶ Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany.
⁸⁷ UMR744 Inserm-Lille2-Institut Pasteur Lille, France.
⁸⁸ Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁸⁹ NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
⁹⁰ Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
⁹¹ BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8QT, UK.
⁹² Cardiovascular Epidemiology and Genetics. IMIM (Institut Hospital del Mar d'Investigacions Mèdiques), Barcelona, Spain.
⁹³ Department of Immunology, Genetics and Pathology, University of Uppsala, Box 815, Biomerical center, 751 08 Uppsala, Sweden.
⁹⁴ Science for Life Laboratory, University of Uppsala, Box 815, Biomerical center, 751 08 Uppsala, Sweden.
⁹⁵ Institut für Integrative und Experimentelle Genomik, Universiät zu Lübeck, RatzeburgerAllee 160, 23538 Lübeck, Germany.
⁹⁶ Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), partner site Hamburg, Kiel, Lübeck, Universität zu Lübeck, Lübeck, Germany.
⁹⁷ Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
⁹⁸ Divisions of Endocrinology/Children's Hospital, Boston, MA 02115, USA.
⁹⁹ Broad Institute of Harvard and MIT, Cambridge, MA 02139 USA.
¹⁰⁰ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
¹⁰¹ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
¹⁰² Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
¹⁰³ Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands.
¹⁰⁴ Toulouse University School of Medicine, Rangueil University Hospital, INSERM UMR1027, Toulouse, France.
¹⁰⁵ Translational Gerontology Branch, National Institute on Aging, Baltimore MD, USA.
¹⁰⁶ Institute of Molecular Medicine, University of Texas Health Science Center at Houston, TX, USA.
¹⁰⁷ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
¹⁰⁸ Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599, USA.
¹⁰⁹ Institute for Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland.
¹¹⁰ Synpromics Ltd, 9 Bioquarter, Little France Road, Edinburgh, EH16 4UX, Scotland.
¹¹¹ University of Michigan Medical School, 7220 MSRB III, Ann Arbor MI 48109, USA.
¹¹² EPIMED Research Centre - Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
¹¹³ Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, Italy.
¹¹⁴ Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
¹¹⁵ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
¹¹⁶ Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹¹⁷ Department of Genetic Epidemiology, Institute of Epidemiology and Preventive Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
¹¹⁸ Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
¹¹⁹ Department of Medicine III, Division Pathobiochemistry, Technische Universität Dresden, Dresden, Germany.
¹²⁰ Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
¹²¹ Icelandic Heart Association, Kopavogur, Iceland.
¹²² Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
¹²³ Institute of Clinical Medicine/Obstetrics and Gynaecology, University of Oulu, Oulu, Finland.
¹²⁴ Medical Research Center, Oulu University Hospital, Oulu, Finland.
¹²⁵ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
¹²⁶ Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU Scotland, UK.
¹²⁷ UREN, INSERM U557, INRA U1125, CNAM, SMBH, Sorbonne Paris Cité, Université Paris 13, Bobigny, France.
¹²⁸ Institute of Biomedicine, University of Oulu, Medical Research Center Oulu and Oulu University Hospital, Finland.
¹²⁹ Biocenter Oulu, P.O.Box 5000, Aapistie 5A, FI-90014 University of Oulu, Finland.
¹³⁰ Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland.
¹³¹ Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, 39100, Italy - affiliated institute of the University of Lübeck, Germany.
¹³² Department of Genetics, Harvard Medical School, Boston, 02115, USA.
¹³³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹³⁴ HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway.
¹³⁵ St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway.
¹³⁶ Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹³⁷ Department of Genetic Medicine, Weill Cornell Medical College Qatar, Doha, Qatar.
¹³⁸ Department of Radiology, Erasmus MC, The Netherlands.
¹³⁹ Department of Neurology, Erasmus MC, University Medical Center Rotterdam, P.O.Box 2040, 3000 CA Rotterdam, The Netherlands.
¹⁴⁰ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany.
¹⁴¹ Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany.
¹⁴² Hannover Medical School, Institute for Human Genetics, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany.
¹⁴³ Kaiser Permanente, Division of Research, Oakland, CA 94612, USA.
¹⁴⁴ Department of Medicine, University of Washington, Seattle, Washington 98101, USA.
¹⁴⁵ Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland.
¹⁴⁶ Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁴⁷ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
¹⁴⁸ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁴⁹ Cardiology Division, Department of Medicine, Massachusetts General Hospital.
¹⁵⁰ Division of Transplantation, Department of Surgery, University of Pennsylvania, PA 19104 USA.
¹⁵¹ Department of Pediatrics, University of Pennsylvania, Philadelphia, PA, USA.
¹⁵² Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK.
¹⁵³ Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, USA.
¹⁵⁴ 1st Cardiology Department, Onassis Cardiac Surgery Center 356, Sygrou Ave, Athens, Greece.
¹⁵⁵ National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, Ducane Road, London W12 0NN, UK.
¹⁵⁶ Department of Medicine, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
¹⁵⁷ MRC Unit for Lifelong Health and Ageing at UCL, London, WC1B 5JU, UK.
¹⁵⁸ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
¹⁵⁹ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
¹⁶⁰ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
¹⁶¹ Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland.
¹⁶² Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁶³ Office of Population Studies Foundation Inc., Talamban, Cebu City, 6000, Philippines.
¹⁶⁴ Department of Anthropology, Sociology, and History, University of San Carlos, Talamban, Cebu City, 6000, Philippines.
¹⁶⁵ Division of Endocrine and Metabolism, Department of Internal Medicine, Chichung Veterans General Hospital, Taichung 40705, Taiwan.
¹⁶⁶ School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹⁶⁷ Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan.
¹⁶⁸ Population Sciences Branch, National Heart Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁶⁹ Cardiovascular Center, Taichung Veterans General Hospital, Taichung, 40705, Taiwan.
¹⁷⁰ Institute of Clinical Medicine, National Yang Ming University School of Medicine, Taipei 112, Taiwan.
¹⁷¹ Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
¹⁷² European Genomic Institute for Diabetes (EGID), FR 3508 Lille, France.
¹⁷³ Centre National de la Recherche Scientifique (CNRS) UMR 8199, Lille Pasteur Institute, 1 rue du Prof Calmette, 59019 Lille Cedex, France.
¹⁷⁴ Lille 2 University, Lille, France.
¹⁷⁵ Center for Evidence-based Healthcare, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany.
¹⁷⁶ Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany.
¹⁷⁷ Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig-Maximilians-Universität, München 81377, Germany.
¹⁷⁸ Neurology Unit, University of Cambridge, R3, Box 83, Cambridge Biomedical Campus, Cambridge, Cb2 0QQ, UK.
¹⁷⁹ Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece.
¹⁸⁰ INSERM U1142 LIMICS, UMR_S 1142 Sorbonne Universités, UPMC Université Paris 06, Université Paris 13, Paris, France.
¹⁸¹ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹⁸² Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie 8, 37134 Verona, Italy.
¹⁸³ Department of Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁸⁴ Unit of General Practice, Oulu University Hospital, Oulu, Finland.
¹⁸⁵ Department of Medicine, Program for Personalized and Genomic Medicine, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
¹⁸⁶ Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, 1200 Pressler St., Suite 453E, Houston, TX 77030, USA.
¹⁸⁷ Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monseratto, Monserrato, Cagliari 09042, Italy.
¹⁸⁸ Department of Cardiology, School of Medicine, University of Tampere, Tampere 33014, Finland.
¹⁸⁹ School of Medicine, University of Tampere, Tampere 33014, Finland.
¹⁹⁰ National Heart, Lung and Blood Institute, Division of Intramural Research, Bethesda, MD, USA.
¹⁹¹ Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.
¹⁹² Divisions of Endocrinology, Children's Hospital Boston, Massachusetts 02115, USA.
¹⁹³ Genetics and Program in Genomics, Children's Hospital Boston, Massachusetts 02115, USA.
¹⁹⁴ Department of Psychiatry, EMGO Institute, Neuroscience Campus, VU University Medical Centre, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
¹⁹⁵ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
¹⁹⁶ Department of Psychiatry, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
¹⁹⁷ International Centre for Circulatory Health, Imperial College London, W2 1PG, UK.
¹⁹⁸ Department of Neurology, General Central Hospital, Bolzano, 39100, Italy.
¹⁹⁹ Department of Neurology, University of Lübeck, Lübeck, Germany.
²⁰⁰ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²⁰¹ Department of Health Services, University of Washington, Seattle, WA.
²⁰² Group Health Research Institute, Group Health Cooperative, Seattle, WA.
²⁰³ Division of Biostatistics, Washington University School of Medicine, Saint Louis, MO, 63110, USA.
²⁰⁴ Center for Non-Communicable Diseases, Karachi, Pakistan.
²⁰⁵ Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
²⁰⁶ Institute of Physiology, University Medicine Greifswald, Greifswald, Germany.
²⁰⁷ Department of Biostatistics, University of Washington, Seattle, WA, USA.
²⁰⁸ University of Ottawa Heart Institute, Cardiovascular Research Methods Centre Ontario, Canada.
²⁰⁹ Ruddy Canadian Cardiovascular Genetics Centre, Ontario, Canada.
²¹⁰ National Heart, Lung, and Blood Institute, 6701 Rockledge Ave., Bethesda, MD 20892, USA.
²¹¹ Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK.
²¹² South Karelia Central Hospital, Lappeenranta, Finland.
²¹³ Deutsches Herzzentrum München, Germany.
²¹⁴ Technische Universität München, Germany.
²¹⁵ Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK), München, Germany.
²¹⁶ Munich Heart Alliance, Germany.
²¹⁷ Center For Life-course Health Research, P.O.Box 5000, FI-90014 University of Oulu, Finland.
²¹⁸ College of Medicine, National Defense Medical Center, Taipei, Taiwan.
²¹⁹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore 117597.
²²⁰ University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland.
²²¹ Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.
²²² Department of Haematology, University of Cambridge, Cambridge, UK.
²²³ Department of Medicine, National University of Singapore and National University Health System, Singapore 119228, Singapore.
²²⁴ Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 21224, USA.
²²⁵ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
²²⁶ Department of Health Sciences, University of Leicester, University Rd, Leicester LE1 7RH, UK.
²²⁷ Department of internal medicine, Erasmus MC, Rotterdam, 3000CA, The Netherlands.
²²⁸ Department of Public Health and Clinical Nutrition, University of Eastern Finland, Finland.
²²⁹ Research Unit, Kuopio University Hospital, Kuopio, Finland.
²³⁰ Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.
²³¹ Johns Hopkins Medical Institutions, 1830 East Monument St., Baltimore, MD 21287, USA.
²³² Centre of Medical Systems Biology (CMSB 1-2), NGI Erasmus Medical Center, Rotterdam, The Netherlands.
²³³ Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands.
²³⁴ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
²³⁵ Section of Preventive medicine, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
²³⁶ Cardiology, Department of Medicine, Boston University School of Medicine, Boston, 02446 MA, USA.
²³⁷ Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
²³⁸ Department of Internal medicine, University Hospital Lausanne, Lausanne, Switzerland.
²³⁹ Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Strasbourg, France.
²⁴⁰ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
²⁴¹ University Medical Center Groningen, University of Groningen, Groningen, 9700RB, The Netherlands.
²⁴² Epidemiology Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica.
²⁴³ Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
²⁴⁴ Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
²⁴⁵ MRC Cancer Unit, University of Cambridge, Cambridge, UK.
²⁴⁶ Department of Epidemiology and Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, OH, 44106, USA.
²⁴⁷ Ministry of Health, Victoria, Republic of Seychelles.
²⁴⁸ Department of Biostatistics and Epidemiology, University of Pennsylvania, USA.
²⁴⁹ MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London W2 1PG, UK.
²⁵⁰ Enterprise Informatics, Illumina Inc., Santa Clara CA, 95050, USA.
²⁵¹ Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
²⁵² Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
²⁵³ Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen, 9711, The Netherlands.
²⁵⁴ Dept Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
²⁵⁵ Department of Medicine, Central Finland Health Care District, Jyväskylä, Finland.
²⁵⁶ Dasman Diabetes Institute, Dasman, 15462 Kuwait.
²⁵⁷ Saudi Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
²⁵⁸ Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria.
²⁵⁹ Department of Medicine, Columbia University, 622 West 168th St., New York, NY 10032, USA.
²⁶⁰ Synlab Academy, Synlab Services GmbH, P5, 7, 68161 Mannheim, Germany.
²⁶¹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.
²⁶² Unit of Primary Care, Oulu University Hospital, Kajaanintie 50, P.O.Box 20, FI-90220 Oulu, 90029 OYS, Finland.
²⁶³ Grosshadern, Klinikum, München 81377, Germany.
²⁶⁴ The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁶⁵ Mindich Child health Development Institute, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
²⁶⁶ Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah 21589, Saudi Arabia.
²⁶⁷ Department of Biostatistics, University of Liverpool, Liverpool L69 3GA, UK.

^# Contributed equally.

PMID: 27618452
PMCID: PMC5042863
DOI: 10.1038/ng.3667

Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

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Figures

**Figure 1. Manhattan plots for SBP and DBP from the stage 4 Cardio-MetaboChip-wide meta-analysis**
P values (expressed as -log₁₀P) are plotted by physical genomic position labeled by chromosome. SNPs in new loci (3.5MB window around the index SNP), identified in this study, are labeled in dark red (SBP) or dark blue (DBP); SNPs in previously known loci are labeled in orange (SBP) or light blue (DBP). The locus names are indicated. The grey crosses indicate genomic positions at which the y-axis was truncated (SNPs with P < 10⁻¹⁵).

**Figure 2. Enrichment of DNAse hypersensitive sites among BP loci in different cell-types**
Enrichment analyses of SBP or DBP associated loci according to discovery P value using narrow peaks (panel A) or broad peaks (panel B). SNPs were selected according to different P value cutoffs (x-axis) and a fold enrichment of overlap with DNAse hypersensitive sites compared to unrelated GWAS SNPs was calculated (y-axis) (see **Supplementary Note**). The 12 endothelial cell-lines are indicated in color and for each endothelial cell-type the rank using the 10⁻¹⁴ P value cutoff is indicated. EC denotes endothelial cells.

See this image and copyright information in PMC

Comment in

Genetics: Genetic factors in the regulation of blood pressure.
Palmer ND, Freedman BI. Palmer ND, et al. Nat Rev Nephrol. 2016 Dec;12(12):716-717. doi: 10.1038/nrneph.2016.150. Epub 2016 Oct 17. Nat Rev Nephrol. 2016. PMID: 27748393 No abstract available.
Genetics of Blood Pressure: New Insights Into a Complex Trait.
Bress AP, Irvin MR, Muntner P. Bress AP, et al. Am J Kidney Dis. 2017 Jun;69(6):723-725. doi: 10.1053/j.ajkd.2017.02.365. Epub 2017 Apr 7. Am J Kidney Dis. 2017. PMID: 28396107 Free PMC article. No abstract available.

References

1. Johnson T, et al. Blood Pressure Loci Identified with a Gene-Centric Array. The American Journal of Human Genetics. 2011;89:1–13. - PMC - PubMed
1. Newton-Cheh C, et al. Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure. Nature genetics. 2009;41:348–53. - PMC - PubMed
1. Franceschini N, et al. Genome-wide association analysis of blood-pressure traits in African- ancestry individuals reveals common associated genes in African and non-African populations. Am J Hum Genet. 2013;93:545–54. - PMC - PubMed
1. Ganesh SK, et al. Effects of long-term averaging of quantitative blood pressure traits on the detection of genetic associations. Am J Hum Genet. 2014;95:49–65. - PMC - PubMed
1. Ehret GB, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478:103–109. - PMC - PubMed

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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

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