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

Wellcome Trust Case Control Consortium; C. Newton-Cheh; T. Johnson; V. Gateva; M. D. Tobin; M. Bochud; L. Coin; S. S. Najjar; J. H. Zhao; S. C. Heath; S. Eyheramendy; K. Papadakis; B. F. Voight; L. J. Scott; F. Zhang; M. Farrall; T. Tanaka; C. Wallace; J. C. Chambers; K. T. Khaw; P. Nilsson; P. van der Harst; S. Polidoro; D. E. Grobbee; N. C. Onland-Moret; M. L. Bots; L. V. Wain; K. S. Elliott; A. Teumer; J. Luan; G. Lucas; J. Kuusisto; P. R. Burton; D. Hadley; W. L. McArdle; M. Brown; A. Dominiczak; S. J. Newhouse; N. J. Samani; J. Webster; E. Zeggini; J. S. Beckmann; S. Bergmann; N. Lim; K. Song; P. Vollenweider; G. Waeber; D. M. Waterworth; X. Yuan; Paul O'Reilly; Gerome Breen; Allan Young

doi:10.1038/ng.388

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

Wellcome Trust Case Control Consortium, C. Newton-Cheh, T. Johnson, V. Gateva, M. D. Tobin, M. Bochud, L. Coin, S. S. Najjar, J. H. Zhao, S. C. Heath, S. Eyheramendy, K. Papadakis, B. F. Voight, L. J. Scott, F. Zhang, M. Farrall, T. Tanaka, C. Wallace, J. C. Chambers, K. T. KhawP. Nilsson, P. van der Harst, S. Polidoro, D. E. Grobbee, N. C. Onland-Moret, M. L. Bots, L. V. Wain, K. S. Elliott, A. Teumer, J. Luan, G. Lucas, J. Kuusisto, P. R. Burton, D. Hadley, W. L. McArdle, M. Brown, A. Dominiczak, S. J. Newhouse, N. J. Samani, J. Webster, E. Zeggini, J. S. Beckmann, S. Bergmann, N. Lim, K. Song, P. Vollenweider, G. Waeber, D. M. Waterworth, X. Yuan, Paul O'Reilly, Gerome Breen, Allan Young

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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.

Original language	English
Pages (from-to)	666-676
Number of pages	11
Journal	Nature Genetics
Volume	41
Issue number	6
DOIs	https://doi.org/10.1038/ng.388
Publication status	Published - Jun 2009

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Wellcome Trust Case Control Consortium, Newton-Cheh, C., Johnson, T., Gateva, V., Tobin, M. D., Bochud, M., Coin, L., Najjar, S. S., Zhao, J. H., Heath, S. C., Eyheramendy, S., Papadakis, K., Voight, B. F., Scott, L. J., Zhang, F., Farrall, M., Tanaka, T., Wallace, C., Chambers, J. C., ... Young, A. (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics, 41(6), 666-676. https://doi.org/10.1038/ng.388

@article{211d490b5bd14a30aa16ef4c724d10a6,

title = "Genome-wide association study identifies eight loci associated with blood pressure",

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.",

author = "{Wellcome Trust Case Control Consortium} and C. Newton-Cheh and T. Johnson and V. Gateva and Tobin, {M. D.} and M. Bochud and L. Coin and Najjar, {S. S.} and Zhao, {J. H.} and Heath, {S. C.} and S. Eyheramendy and K. Papadakis and Voight, {B. F.} and Scott, {L. J.} and F. Zhang and M. Farrall and T. Tanaka and C. Wallace and Chambers, {J. C.} and Khaw, {K. T.} and P. Nilsson and {van der Harst}, P. and S. Polidoro and Grobbee, {D. E.} and Onland-Moret, {N. C.} and Bots, {M. L.} and Wain, {L. V.} and Elliott, {K. S.} and A. Teumer and J. Luan and G. Lucas and J. Kuusisto and Burton, {P. R.} and D. Hadley and McArdle, {W. L.} and M. Brown and A. Dominiczak and Newhouse, {S. J.} and Samani, {N. J.} and J. Webster and E. Zeggini and Beckmann, {J. S.} and S. Bergmann and N. Lim and K. Song and P. Vollenweider and G. Waeber and Waterworth, {D. M.} and X. Yuan and Paul O'Reilly and Gerome Breen and Allan Young",

year = "2009",

month = jun,

doi = "10.1038/ng.388",

language = "English",

volume = "41",

pages = "666--676",

journal = "Nature Genetics",

issn = "1546-1718",

publisher = "Nature Research",

number = "6",

}

Wellcome Trust Case Control Consortium, 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, 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 , O'Reilly, P , Breen, G & Young, A 2009, 'Genome-wide association study identifies eight loci associated with blood pressure', Nature Genetics, vol. 41, no. 6, pp. 666-676. https://doi.org/10.1038/ng.388

TY - JOUR

T1 - Genome-wide association study identifies eight loci associated with blood pressure

AU - Wellcome Trust Case Control Consortium

AU - Newton-Cheh, C.

AU - Johnson, T.

AU - Gateva, V.

AU - Tobin, M. D.

AU - Bochud, M.

AU - Coin, L.

AU - Najjar, S. S.

AU - Zhao, J. H.

AU - Heath, S. C.

AU - Eyheramendy, S.

AU - Papadakis, K.

AU - Voight, B. F.

AU - Scott, L. J.

AU - Zhang, F.

AU - Farrall, M.

AU - Tanaka, T.

AU - Wallace, C.

AU - Chambers, J. C.

AU - Khaw, K. T.

AU - Nilsson, P.

AU - van der Harst, P.

AU - Polidoro, S.

AU - Grobbee, D. E.

AU - Onland-Moret, N. C.

AU - Bots, M. L.

AU - Wain, L. V.

AU - Elliott, K. S.

AU - Teumer, A.

AU - Luan, J.

AU - Lucas, G.

AU - Kuusisto, J.

AU - Burton, P. R.

AU - Hadley, D.

AU - McArdle, W. L.

AU - Brown, M.

AU - Dominiczak, A.

AU - Newhouse, S. J.

AU - Samani, N. J.

AU - Webster, J.

AU - Zeggini, E.

AU - Beckmann, J. S.

AU - Bergmann, S.

AU - Lim, N.

AU - Song, K.

AU - Vollenweider, P.

AU - Waeber, G.

AU - Waterworth, D. M.

AU - Yuan, X.

AU - O'Reilly, Paul

AU - Breen, Gerome

AU - Young, Allan

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

U2 - 10.1038/ng.388

DO - 10.1038/ng.388

M3 - Article

SN - 1546-1718

VL - 41

SP - 666

EP - 676

JO - Nature Genetics

JF - Nature Genetics

IS - 6

ER -

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

Abstract

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