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PMID: 19430483 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Genome-wide association study identifies eight loci associated with blood pressure.

Nature genetics ·Vol. 41 ·No. 6 ·2009-06-00 ·Pages 666-76

Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Tanaka T, Wallace C, Chambers JC, Khaw KT, Nilsson P, van der Harst P, Polidoro S, Grobbee DE, Onland-Moret NC, Bots ML, Wain LV, Elliott KS, Teumer A, Luan J, Lucas G, Kuusisto J, Burton PR, Hadley D, McArdle WL, Wellcome Trust Case Control Consortium, Brown M, Dominiczak A, Newhouse SJ, Samani NJ, Webster J, Zeggini E, Beckmann JS, Bergmann S, Lim N, Song K, Vollenweider P, Waeber G, Waterworth DM, Yuan X, Groop L, Orho-Melander M, Allione A, Di Gregorio A, Guarrera S, Panico S, Ricceri F, Romanazzi V, Sacerdote C, Vineis P, Barroso I, Sandhu MS, Luben RN, Crawford GJ, Jousilahti P, Perola M, Boehnke M, Bonnycastle LL, Collins FS, Jackson AU, Mohlke KL, Stringham HM, Valle TT, Willer CJ, Bergman RN, Morken MA, Döring A, Gieger C, Illig T, Meitinger T, Org E, Pfeufer A, Wichmann HE, Kathiresan S, Marrugat J, O'Donnell CJ, Schwartz SM, Siscovick DS, Subirana I, Freimer NB, Hartikainen AL, McCarthy MI, O'Reilly PF, Peltonen L, Pouta A, de Jong PE, Snieder H, van Gilst WH, Clarke R, Goel A, Hamsten A, Peden JF, Seedorf U, Syvänen AC, Tognoni G, Lakatta EG, Sanna S, Scheet P, Schlessinger D, Scuteri A, Dörr M, Ernst F, Felix SB, Homuth G, Lorbeer R, Reffelmann T, Rettig R, Völker U, Galan P, Gut IG, Hercberg S, Lathrop GM, Zelenika D, Deloukas P, Soranzo N, Williams FM, Zhai G, Salomaa V, Laakso M, Elosua R, Forouhi NG, Völzke H, Uiterwaal CS, van der Schouw YT, Numans ME, Matullo G, Navis G, Berglund G, Bingham SA, Kooner JS, Connell JM, Bandinelli S, Ferrucci L, Watkins H, Spector TD, Tuomilehto J, Altshuler D, Strachan DP, Laan M, Meneton P, Wareham NJ, Uda M, Jarvelin MR, Mooser V, Melander O, Loos RJ, Elliott P, Abecasis GR, Caulfield M, Munroe PB

Abstract

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

MeSH Terms

Adaptor Proteins, Signal Transducing Blood Pressure/genetics Cardiovascular Diseases/genetics,physiopathology Chromosome Mapping Cytochrome P-450 CYP1A2/genetics DNA-Binding Proteins/genetics Diastole/genetics Europe Fibroblast Growth Factor 5/genetics Genetic Variation Genome-Wide Association Study Humans India Intracellular Signaling Peptides and Proteins Methylenetetrahydrofolate Reductase (NADPH2)/genetics Open Reading Frames/genetics Phospholipase C delta/genetics Polymorphism, Single Nucleotide Proteins/genetics Steroid 17-alpha-Hydroxylase/genetics Systole/genetics Whites/genetics

Chemicals

Adaptor Proteins, Signal Transducing DNA-Binding Proteins FGF5 protein, human Intracellular Signaling Peptides and Proteins Proteins SH2B3 protein, human ZNF652 protein, human Fibroblast Growth Factor 5 CYP1A2 protein, human Cytochrome P-450 CYP1A2 CYP17A1 protein, human Steroid 17-alpha-Hydroxylase Methylenetetrahydrofolate Reductase (NADPH2) PLCD3 protein, human Phospholipase C delta

Authors & Affiliations

159 authors, click to expand affiliations / ORCID

Newton-Cheh Christopher

Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [email protected]

Johnson Toby

Gateva Vesela

Tobin Martin D

Bochud Murielle

Coin Lachlan

Najjar Samer S

Zhao Jing Hua

Heath Simon C

Eyheramendy Susana

Papadakis Konstantinos

Voight Benjamin F

Scott Laura J

Zhang Feng

Farrall Martin

Tanaka Toshiko

Wallace Chris

Chambers John C

Khaw Kay-Tee

Nilsson Peter

van der Harst Pim

Polidoro Silvia

Grobbee Diederick E

Onland-Moret N Charlotte

Bots Michiel L

Wain Louise V

Elliott Katherine S

Teumer Alexander

Luan Jian'an

Lucas Gavin

Kuusisto Johanna

Burton Paul R

Hadley David

McArdle Wendy L

Wellcome Trust Case Control Consortium

Brown Morris

Dominiczak Anna

Newhouse Stephen J

Samani Nilesh J

Webster John

Zeggini Eleftheria

Beckmann Jacques S

Bergmann Sven

Lim Noha

Song Kijoung

Vollenweider Peter

Waeber Gerard

Waterworth Dawn M

Yuan Xin

Groop Leif

Orho-Melander Marju

Allione Alessandra

Di Gregorio Alessandra

Guarrera Simonetta

Panico Salvatore

Ricceri Fulvio

Romanazzi Valeria

Sacerdote Carlotta

Vineis Paolo

Barroso Inês

Sandhu Manjinder S

Luben Robert N

Crawford Gabriel J

Jousilahti Pekka

Perola Markus

Boehnke Michael

Bonnycastle Lori L

Collins Francis S

Jackson Anne U

Mohlke Karen L

Stringham Heather M

Valle Timo T

Willer Cristen J

Bergman Richard N

Morken Mario A

Döring Angela

Gieger Christian

Illig Thomas

Meitinger Thomas

Org Elin

Pfeufer Arne

Wichmann H Erich

Kathiresan Sekar

Marrugat Jaume

O'Donnell Christopher J

Schwartz Stephen M

Siscovick David S

Subirana Isaac

Freimer Nelson B

Hartikainen Anna-Liisa

McCarthy Mark I

O'Reilly Paul F

Peltonen Leena

Pouta Anneli

de Jong Paul E

Snieder Harold

van Gilst Wiek H

Clarke Robert

Goel Anuj

Hamsten Anders

Peden John F

Seedorf Udo

Syvänen Ann-Christine

Tognoni Giovanni

Lakatta Edward G

Sanna Serena

Scheet Paul

Schlessinger David

Scuteri Angelo

Dörr Marcus

Ernst Florian

Felix Stephan B

Homuth Georg

Lorbeer Roberto

Reffelmann Thorsten

Rettig Rainer

Völker Uwe

Galan Pilar

Gut Ivo G

Hercberg Serge

Lathrop G Mark

Zelenika Diana

Deloukas Panos

Soranzo Nicole

Williams Frances M

Zhai Guangju

Salomaa Veikko

Laakso Markku

Elosua Roberto

Forouhi Nita G

Völzke Henry

Uiterwaal Cuno S

van der Schouw Yvonne T

Numans Mattijs E

Matullo Giuseppe

Navis Gerjan

Berglund Göran

Bingham Sheila A

Kooner Jaspal S

Connell John M

Bandinelli Stefania

Ferrucci Luigi

Watkins Hugh

Spector Tim D

Tuomilehto Jaakko

Altshuler David

Strachan David P

Laan Maris

Meneton Pierre

Wareham Nicholas J

Uda Manuela

Jarvelin Marjo-Riitta

Mooser Vincent

Melander Olle

Loos Ruth J F

Elliott Paul

Abecasis Gonçalo R

Caulfield Mark

Munroe Patricia B

Investigators

258 investigators, click to expand

Burton Paul R

Clayton David G

Cardon Lon R

Craddock Nick

Deloukas Panos

Duncanson Audrey

Kwiatkowski Dominic P

McCarthy Mark I

Ouwehand Willem H

Samani Nilesh J

Todd John A

Donnelly Peter

Barrett Jeffrey C

Burton Paul R

Davison Dan

Donnelly Peter

Easton Doug

Evans David

Leung Hin-Tak

Marchini Jonathan L

Morris Andrew P

Spencer I C A

Tobin Martin D

Cardon Lon R

Clayton David G

Attwood Antony P

Boorman James P

Cant Barbara

Everson Ursula

Hussey Judith M

Jolley Jennifer D

Knight Alexandra S

Koch Kerstin

Meech Elizabeth

Nutland Sarah

Prowse Christopher V

Stevens Helen E

Taylor Niall C

Walters Graham R

Walker Neil M

Watkins Nicholas A

Winzer Thilo

Todd John A

Ouwehand Willem H

Jones Richard W

McArdle Wendy L

Ring Susan M

Strachan David P

Pembrey Marcus

Breen Gerome

St Clair David

Caesar Sian

Gordon-Smith Katherine

Jones Lisa

Fraser Christine

Green Elaine K

Grozeva Detelina

Hamshere Marian L

Holmans Peter A

Jones Ian R

Kirov George

Moskvina Valentina

Nikolov Ivan

O'Donovan Michael C

Owen Michael J

Craddock Nick

Collier David A

Elkin Amanda

Farmer Anne

Williamson Richard

McGuffin Peter

Young Allan H

Ferrier I Nicol

Ball Stephen G

Balmforth Anthony J

Barrett Jennifer H

Bishop D Timothy

Iles Mark M

Maqbool Azhar

Yuldasheva Nadira

Hall Alistair S

Braund Peter S

Burton Paul R

Dixon Richard J

Mangino Massimo

Stevens Suzanne

Tobin Martin D

Thompson John R

Samani Nilesh J

Bredin Francesca

Tremelling Mark

Parkes Miles

Drummond Hazel

Lees Charles W

Nimmo Elaine R

Satsangi Jack

Fisher Sheila A

Forbes Alastair

Lewis Cathryn M

Onnie Clive M

Prescott Natalie J

Sanderson Jeremy

Mathew Christopher G

Barbour Jamie

Mohiuddin M Khalid

Todhunter Catherine E

Mansfield John C

Ahmad Tariq

Cummings Fraser R

Jewell Derek P

Webster John

Brown Morris J

Clayton David G

Lathrop G Mark

Connell John

Dominiczak Anna

Samani Nilesh J

Braga Marcano Carolina A

Burke Beverley

Dobson Richard

Gungadoo Johannie

Lee Kate L

Munroe Patricia B

Newhouse Stephen J

Onipinla Abiodun

Wallace I

Xue Mingzhan

Caulfield Mark

Farrall Martin

Barton Anne

Bruce Ian N

Donovan Hannah

Eyre Steve

Gilbert Paul D

Hider Samantha L

Hinks Anne M

John Sally L

Potter Catherine

Silman Alan J

Symmons Deborah P M

Thomson Wendy

Worthington Jane

Clayton David G

Dunger David B

Nutland Sarah

Stevens Helen E

Walker Neil M

Widmer Barry

Todd John A

Frayling Timothy M

Freathy Rachel M

Lango Hana

Perry John R B

Shields Beverley M

Weedon Michael N

Hattersley Andrew T

Hitman Graham A

Walker Mark

Elliott Kate S

Groves Christopher J

Lindgren Cecilia M

Rayner Nigel W

Timpson Nicholas J

Zeggini Eleftheria

McCarthy Mark I

Newport Melanie

Sirugo Giorgio

Lyons Emily

Vannberg Fredrik

Hill Adrian V S

Bradbury Linda A

Farrar Claire

Pointon Jennifer J

Wordsworth Paul

Brown Matthew A

Franklyn Jayne A

Heward Joanne M

Simmonds Matthew J

Gough Stephen C L

Seal Sheila

Stratton Michael R

Rahman Nazneen

Ban Maria

Goris An

Sawcer Stephen J

Compston Alastair

Conway David

Jallow Muminatou

Newport Melanie

Sirugo Giorgio

Rockett Kirk A

Kwiatkowski Dominic P

Bryan Claire

Bumpstead Suzannah J

Chaney Amy

Downes Kate

Ghori Jilur

Gwilliam Rhian

Hunt Sarah E

Inouye Michael

Keniry Andrew

King Emma

McGinnis Ralph

Potter Simon

Ravindrarajah Rathi

Whittaker Pamela

Withers David

Deloukas Panos

Leung Hin-Tak

Nutland Sarah

Stevens Helen E

Walker Neil M

Todd John A

Easton Doug

Clayton David G

Burton Paul R

Tobin Martin D

Barrett Jeffrey C

Evans David

Morris Andrew P

Cardon Lon R

Cardin Niall J

Davison Dan

Ferreira Teresa

Pereira-Gale Joanne

Hallgrimsdóttir Ingeleif B

Howie Bryan N

Marchini Jonathan L

Spencer I C A

Su Zhan

Teo Yik Ying

Vukcevic Damjan

Donnelly Peter

Bentley David

Brown Matthew A

Cardon Lon R

Caulfield Mark

Clayton David G

Compston Alistair

Craddock Nick

Deloukas Panos

Donnelly Peter

Farrall Martin

Gough Stephen C L

Hall Alistair S

Hattersley Andrew T

Hill Adrian V S

Kwiatkowski Dominic P

Mathew Christopher G

McCarthy Mark I

Ouwehand Willem H

Parkes Miles

Pembrey Marcus

Rahman Nazneen

Samani Nilesh J

Stratton Michael R

Todd John A

Worthington Jane

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Article Info

Journal

Nature genetics

Abbr.

Nat Genet

ISSN

1546-1718

DOI

10.1038/ng.361

[email protected]

Published

2009-06-00

Epub

2009-00-10

Pages

666-76

Language

English

Region

United States

NLM ID

9216904

PMCID

PMC2891673

Subset

Grants

Medical Research Council · G0400874 · United Kingdom

NIDDK NIH HHS · R56 DK062370 · United States

Wellcome Trust · 079557 · United Kingdom

Wellcome Trust · 070191/Z/03/Z · United Kingdom

NIDDK NIH HHS · R01 DK072193 · United States

Medical Research Council · MC_U105630924 · United Kingdom

British Heart Foundation · PG02/128 · United Kingdom

Medical Research Council · G0401527 · United Kingdom

Medical Research Council · G0800675 · United Kingdom

Wellcome Trust · 079895 · United Kingdom

Wellcome Trust · WT088885/Z/09/Z · United Kingdom

Medical Research Council · G9521010 · United Kingdom

NHLBI NIH HHS · R01 HL056931-02 · United States

Medical Research Council · G0801056 · United Kingdom

NIMHD NIH HHS · 263MD821336 · United States

NHLBI NIH HHS · R01 HL087679 · United States

NIA NIH HHS · N01-AG-1-2109 · United States

NCRR NIH HHS · U54RR020278 · United States

NHLBI NIH HHS · R01 HL087676 · United States

British Heart Foundation · SP/04/002 · United Kingdom

NHLBI NIH HHS · K23HL80025 · United States

Wellcome Trust · 088885 · United Kingdom

Wellcome Trust · 068545/Z/02 · United Kingdom

British Heart Foundation · FS/05/061/19501 · United Kingdom

NHLBI NIH HHS · K23HL083102 · United States

NHLBI NIH HHS · K23 HL080025-04 · United States

NIDA NIH HHS · U54DA021519 · United States

Wellcome Trust · 077011 · United Kingdom

NHLBI NIH HHS · K23 HL083102 · United States

NHGRI NIH HHS · 1Z01HG000024 · United States

Medical Research Council · MC_U137686857 · United Kingdom

Wellcome Trust · 077016 · United Kingdom

NIDDK NIH HHS · R01 DK062370 · United States

NIA NIH HHS · N01AG-916413 · United States

NIA NIH HHS · N01AG-821336 · United States

NIDDK NIH HHS · U01 DK062418 · United States

Wellcome Trust · 076113 · United Kingdom

NIEHS NIH HHS · P30ES007033 · United States

NIDDK NIH HHS · DK072193 · United States

PHS HHS · 263-MA-410953 · United States

Medical Research Council · G9521010D · United Kingdom

NHLBI NIH HHS · R01HL087676 · United States

NICHD NIH HHS · N01-HD-1-3107 · United States

NIEHS NIH HHS · P30 ES007033 · United States

Medical Research Council · G0701863 · United Kingdom

Medical Research Council · G0800759 · United Kingdom

Intramural NIH HHS · Z01 HG000024 · United States

Medical Research Council · 85374 · United Kingdom

Wellcome Trust · 090532 · United Kingdom

Wellcome Trust · 077016/Z/05/Z · United Kingdom

Chief Scientist Office · CZB/4/540 · United Kingdom

NIMHD NIH HHS · 263MD916413 · United States

NIDDK NIH HHS · U01 DK062370 · United States

NHLBI NIH HHS · R01 HL056931-04 · United States

NHLBI NIH HHS · R01HL056931 · United States

NIDDK NIH HHS · DK062370 · United States

Medical Research Council · G0000934 · United Kingdom

NHLBI NIH HHS · R01 HL056931-03 · United States

NIMH NIH HHS · RL1MH083268 · United States

NIDDK NIH HHS · U01DK062418 · United States

Wellcome Trust · 089061 · United Kingdom

Medical Research Council · G0501942 · United Kingdom

NIMH NIH HHS · RL1 MH083268 · United States

Medical Research Council · MC_QA137934 · United Kingdom

NIDA NIH HHS · U54 DA021519 · United States

Wellcome Trust · 061858 · United Kingdom

Medical Research Council · MC_U106188470 · United Kingdom

Cancer Research UK · 10589 · United Kingdom

NCRR NIH HHS · U54 RR020278 · United States

NHLBI NIH HHS · K23 HL080025 · United States

Wellcome Trust · 076113/B/04/Z · United Kingdom

Medical Research Council · G0600329 · United Kingdom

NHLBI NIH HHS · R01HL087679 · United States

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