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

TitleGenome-wide association study identifies eight loci associated with blood pressure.
Publication TypeJournal Article
Year of Publication2009
AuthorsNewton-Cheh, C, Johnson, T, Gateva, V, Tobin, MD, Bochud, M, Coin, L, Najjar, SS, Zhao, JHua, Heath, SC, Eyheramendy, S, Papadakis, K, Voight, BF, Scott, LJ, Zhang, F, Farrall, M, Tanaka, T, Wallace, C, Chambers, JC, Khaw, K-T, Nilsson, P, van der Harst, P, Polidoro, S, Grobbee, DE, N Onland-Moret, C, Bots, ML, Wain, LV, Elliott, KS, Teumer, A, Luan, J'an, Lucas, G, Kuusisto, J, Burton, PR, Hadley, D, McArdle, WL, 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, H Wichmann, E, Kathiresan, S, Marrugat, J, O'Donnell, CJ, Schwartz, SM, Siscovick, DS, Subirana, I, Freimer, NB, Hartikainen, A-L, 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, A-C, 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, G Lathrop, M, 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, M-R, Mooser, V, Melander, O, Loos, RJF, Elliott, P, Abecasis, GR, Caulfield, M, Munroe, PB
Corporate Authors
JournalNat Genet
Volume41
Issue6
Pagination666-76
Date Published2009 Jun
ISSN1546-1718
KeywordsBlood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cytochrome P-450 CYP1A2, Diastole, DNA-Binding Proteins, Europe, European Continental Ancestry Group, Fibroblast Growth Factor 5, Genetic Variation, Genome-Wide Association Study, Humans, India, Methylenetetrahydrofolate Reductase (NADPH2), Open Reading Frames, Phospholipase C delta, Polymorphism, Single Nucleotide, Proteins, Steroid 17-alpha-Hydroxylase, Systole
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.

DOI10.1038/ng.361
Alternate JournalNat. Genet.
Citation Key10.1038/ng.361
PubMed ID19430483
PubMed Central IDPMC2891673
Grant ListFS/05/061/19501 / / British Heart Foundation / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
R01 HL056931-02 / HL / NHLBI NIH HHS / United States
G0801056 / / Medical Research Council / United Kingdom
G0400874 / / Medical Research Council / United Kingdom
R56 DK062370 / DK / NIDDK NIH HHS / United States
079557 / / Wellcome Trust / United Kingdom
263MD821336 / MD / NIMHD NIH HHS / United States
SP/04/002 / / British Heart Foundation / United Kingdom
R01 HL087679 / HL / NHLBI NIH HHS / United States
R01 HL087676 / HL / NHLBI NIH HHS / United States
N01-AG-1-2109 / AG / NIA NIH HHS / United States
U54RR020278 / RR / NCRR NIH HHS / United States
K23HL80025 / HL / NHLBI NIH HHS / United States
WT088885/Z/09/Z / / Wellcome Trust / United Kingdom
088885 / / Wellcome Trust / United Kingdom
079895 / / Wellcome Trust / United Kingdom
G9521010D / / Medical Research Council / United Kingdom
R01 DK072193 / DK / NIDDK NIH HHS / United States
K23HL083102 / HL / NHLBI NIH HHS / United States
K23 HL080025-04 / HL / NHLBI NIH HHS / United States
MC_U105630924 / / Medical Research Council / United Kingdom
U54DA021519 / DA / NIDA NIH HHS / United States
077011 / / Wellcome Trust / United Kingdom
K23 HL083102 / HL / NHLBI NIH HHS / United States
1Z01HG000024 / HG / NHGRI NIH HHS / United States
MC_U137686857 / / Medical Research Council / United Kingdom
077016 / / Wellcome Trust / United Kingdom
R01 DK062370 / DK / NIDDK NIH HHS / United States
N01AG-916413 / AG / NIA NIH HHS / United States
PG02/128 / / British Heart Foundation / United Kingdom
P30ES007033 / ES / NIEHS NIH HHS / United States
DK072193 / DK / NIDDK NIH HHS / United States
N01AG-821336 / AG / NIA NIH HHS / United States
U01 DK062418 / DK / NIDDK NIH HHS / United States
076113 / / Wellcome Trust / United Kingdom
/ / Intramural NIH HHS / United States
85374 / / Medical Research Council / United Kingdom
263-MA-410953 / / PHS HHS / United States
N01-HD-1-3107 / HD / NICHD NIH HHS / United States
P30 ES007033 / ES / NIEHS NIH HHS / United States
/ / Cancer Research UK / United Kingdom
R01HL087676 / HL / NHLBI NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
G0501942 / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
G0800759 / / Medical Research Council / United Kingdom
090532 / / Wellcome Trust / United Kingdom
CZB/4/540 / / Chief Scientist Office / United Kingdom
263MD916413 / MD / NIMHD NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
R01 HL056931-04 / HL / NHLBI NIH HHS / United States
R01HL056931 / HL / NHLBI NIH HHS / United States
DK062370 / DK / NIDDK NIH HHS / United States
R01 HL056931-03 / HL / NHLBI NIH HHS / United States
RL1MH083268 / MH / NIMH NIH HHS / United States
U01DK062418 / DK / NIDDK NIH HHS / United States
089061 / / Wellcome Trust / United Kingdom
068545/Z/02 / / Wellcome Trust / United Kingdom
RL1 MH083268 / MH / NIMH NIH HHS / United States
Z01 HG000024 / HG / NHGRI NIH HHS / United States
MC_QA137934 / / Medical Research Council / United Kingdom
U54 DA021519 / DA / NIDA NIH HHS / United States
061858 / / Wellcome Trust / United Kingdom
MC_U106188470 / / Medical Research Council / United Kingdom
076113/B/04/Z / / Wellcome Trust / United Kingdom
10589 / / Cancer Research UK / United Kingdom
077016/Z/05/Z / / Wellcome Trust / United Kingdom
G0000934 / / Medical Research Council / United Kingdom
G0800675 / / Medical Research Council / United Kingdom
U54 RR020278 / RR / NCRR NIH HHS / United States
K23 HL080025 / HL / NHLBI NIH HHS / United States
G0600329 / / Medical Research Council / United Kingdom
070191/Z/03/Z / / Wellcome Trust / United Kingdom
R01HL087679 / HL / NHLBI NIH HHS / United States