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Nat Genet. 2016 Oct;48(10):1171-1184. doi: 10.1038/ng.3667. Epub 2016 Sep 12.

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

Ehret GB#1,2, Ferreira T#3, Chasman DI4,5, Jackson AU6,7, Schmidt EM8, Johnson T9,10, Thorleifsson G11, Luan J12, Donnelly LA13, Kanoni S14, Petersen AK15, Pihur V1, Strawbridge RJ16,17, Shungin D18,19,20, Hughes MF21, Meirelles O22, Kaakinen M23, Bouatia-Naji N24,25, Kristiansson K26,27, Shah S28, Kleber ME29, Guo X30, Lyytikäinen LP31,32, Fava C33,34, Eriksson N35, Nolte IM36, Magnusson PK37, Salfati EL38, Rallidis LS39, Theusch E40, Smith AJP41, Folkersen L16, Witkowska K9,42, Pers TH43,44,45,46,47, Joehanes R48, Kim SK49, Lataniotis L14, Jansen R50, Johnson AD48,51, Warren H9,42, Kim YJ52, Zhao W53, Wu Y54, Tayo BO55, Bochud M56; CHARGE-EchoGen consortium; CHARGE-HF consortium; Wellcome Trust Case Control Consortium, Absher D57, Adair LS58, Amin N59, Arking DE1, Axelsson T60, Baldassarre D61,62, Balkau B63, Bandinelli S64, Barnes MR14,42, Barroso I65,66,67, Bevan S68, Bis JC69, Bjornsdottir G11, Boehnke M6,7, Boerwinkle E70, Bonnycastle LL71, Boomsma DI72, Bornstein SR73, Brown MJ74, Burnier M75, Cabrera CP9,42, Chambers JC76,77,78, Chang IS79, Cheng CY80,81,82, Chines PS71, Chung RH83, Collins FS71, Connell JM84, Döring A85,86, Dallongeville J87, Danesh J88,65,89, de Faire U90, Delgado G29, Dominiczak AF91, Doney ASF13, Drenos F41, Edkins S65, Eicher JD48,51, Elosua R92, Enroth S93,94, Erdmann J95,96, Eriksson P16, Esko T97,98,99, Evangelou E76,100, Evans A21, Fall T101, Farrall M3,102, Felix JF103, Ferrières J104, Ferrucci L105, Fornage M106, Forrester T107, Franceschini N108, Duran OHF103, Franco-Cereceda A100, Fraser RM109,110, Ganesh SK111, Gao H76, Gertow K16,17, Gianfagna F112,113, Gigante B90, Giulianini F4, Goel A3,102, Goodall AH114,115, Goodarzi MO116, Gorski M117,118, Gräßler J119, Groves C120, Gudnason V121,122, Gyllensten U93,94, Hallmans G18, Hartikainen AL123,124, Hassinen M125, Havulinna AS26, Hayward C126, Hercberg S127, Herzig KH128,129,130, Hicks AA131, Hingorani AD28, Hirschhorn JN43,44,45,132, Hofman A103,133, Holmen J134, Holmen OL134,135, Hottenga JJ72, Howard P41, Hsiung CA83, Hunt SC136,137, Ikram MA103,138,139, Illig T140,141,142, Iribarren C143, Jensen RA70,144, Kähönen M145, Kang H6,7, Kathiresan S146,147,148,45,149, Keating BJ150,151, Khaw KT152, Kim YK52, Kim E153, Kivimaki M28, Klopp N140,141, Kolovou G154, Komulainen P125, Kooner JS155,77,78, Kosova G147,146,99, Krauss RM156, Kuh D157, Kutalik Z158,159, Kuusisto J160, Kvaløy K134, Lakka TA161,125,162, Lee NR163,164, Lee IT165,166, Lee WJ167, Levy D48,168, Li X30, Liang KW169,170, Lin H171,48, Lin L2, Lindström J26, Lobbens S172,173,174, Männistö S26, Müller G175, Müller-Nurasyid M15,176,177, Mach F2, Markus HS178, Marouli E14,179, McCarthy MI120, McKenzie CA107, Meneton P180, Menni C181, Metspalu A97, Mijatovic V182, Moilanen L183,184, Montasser ME185, Morris AD13, Morrison AC186, Mulas A187, Nagaraja R22, Narisu N71, Nikus K188,189, O'Donnell CJ190,48,149, O'Reilly PF191, Ong KK12, Paccaud F56, Palmer CD192,193,45, Parsa A185, Pedersen NL37, Penninx BW194,195,196, Perola M26,27,97, Peters A86, Poulter N197, Pramstaller PP131,198,199, Psaty BM69,200,201,202, Quertermous T38, Rao DC203, Rasheed A204, Rayner NWNWR120,3,65, Renström F19,205,18, Rettig R206, Rice KM207, Roberts R208,209, Rose LM4, Rossouw J210, Samani NJ114,211, Sanna S187, Saramies J212, Schunkert H213,214,215,216, Sebert S217,129,162, Sheu WH165,166,218, Shin YA52, Sim X6,7,219, Smit JH194, Smith AV121,122, Sosa MX1, Spector TD181, Stančáková A220, Stanton A221, Stirrups KE14,222, Stringham HM6,7, Sundstrom J60, Swift AJ71, Syvänen AC60, Tai ES223,81,219, Tanaka T105, Tarasov KV224, Teumer A225, Thorsteinsdottir U11,122, Tobin MD226, Tremoli E61,62, Uitterlinden AG103,227, Uusitupa M228,229, Vaez A36,230, Vaidya D231, van Duijn CM103,232, van Iperen EPA233,234, Vasan RS48,235,236, Verwoert GC103, Virtamo J26, Vitart V126, Voight BF45,237, Vollenweider P238, Wagner A239, Wain LV226, Wareham NJ12, Watkins H3,102, Weder AB240, Westra HJ241, Wilks R242, Wilsgaard T243,244, Wilson JF109,126, Wong TY80,81,82, Yang TP14,245, Yao J30, Yengo L172,173,174, Zhang W76,77, Zhao JH12, Zhu X246, Bovet P247,56, Cooper RS55, Mohlke KL54, Saleheen D248,204, Lee JY52, Elliott P76,249, Gierman HJ49,250, Willer CJ8,251,252, Franke L253, Hovingh GK254, Taylor KD30, Dedoussis G179, Sever P197, Wong A157, Lind L60, Assimes TL38, Njølstad I243,244, Schwarz PE73, Langenberg C12, Snieder H36, Caulfield MJ9,42, Melander O33, Laakso M160, Saltevo J255, Rauramaa R125,162, Tuomilehto J26,256,257,258, Ingelsson E101,3, Lehtimäki T31,32, Hveem K134, Palmas W259, März W260,261, Kumari M28, Salomaa V26, Chen YI30, Rotter JI30, Froguel P172,173,174,23, Jarvelin MR217,129,262,249, Lakatta EG224, Kuulasmaa K26, Franks PW19,205,18, Hamsten A16,17, Wichmann HE85,177,263, Palmer CNA13, Stefansson K11,122, Ridker PM4,5, Loos RJF12,264,265, Chakravarti A1, Deloukas P14,266, Morris AP267,3, Newton-Cheh C146,147,45,99, Munroe PB9,42.

Author information

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

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.

PMID:
27618452
PMCID:
PMC5042863
DOI:
10.1038/ng.3667
[Indexed for MEDLINE]
Free PMC Article

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