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

Christopher Newton-Cheh; Toby Johnson; Vesela Gateva; Martin D Tobin; Murielle Bochud; Lachlan Coin; Samer S Najjar; Jing Hua Zhao; Simon C Heath; Susana Eyheramendy; Konstantinos Papadakis; Benjamin F Voight; Laura J Scott; Feng Zhang; Martin Farrall; Toshiko Tanaka; Chris Wallace; John C Chambers; Kay-Tee Khaw; Peter Nilsson; Pim van der Harst; Silvia Polidoro; Diederick E Grobbee; N Charlotte Onland-Moret; Michiel L Bots; Louise V Wain; Katherine S Elliott; Alexander Teumer; Jian'an Luan; Gavin Lucas; Johanna Kuusisto; Paul R Burton; David Hadley; Wendy L McArdle; Morris Brown; Anna Dominiczak; Stephen J Newhouse; Nilesh J Samani; John Webster; Eleftheria Zeggini; Jacques S Beckmann; Sven Bergmann; Noha Lim; Kijoung Song; Peter Vollenweider; Gerard Waeber; Dawn M Waterworth; Xin Yuan; Leif Groop; Marju Orho-Melander; Wellcome Trust Case Control Consortium

doi:10.1038/ng.361

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

Christopher Newton-Cheh, Toby Johnson, Vesela Gateva, Martin D Tobin, Murielle Bochud, Lachlan Coin, Samer S Najjar, Jing Hua Zhao, Simon C Heath, Susana Eyheramendy, Konstantinos Papadakis, Benjamin F Voight, Laura J Scott, Feng Zhang, Martin Farrall, Toshiko Tanaka, Chris Wallace, John C Chambers, Kay-Tee Khaw, Peter NilssonPim van der Harst, Silvia Polidoro, Diederick E Grobbee, N Charlotte Onland-Moret, Michiel L Bots, Louise V Wain, Katherine S Elliott, Alexander Teumer, Jian'an Luan, Gavin Lucas, Johanna Kuusisto, Paul R Burton, David Hadley, Wendy L McArdle, Morris Brown, Anna Dominiczak, Stephen J Newhouse, Nilesh J Samani, John Webster, Eleftheria Zeggini, Jacques S Beckmann, Sven Bergmann, Noha Lim, Kijoung Song, Peter Vollenweider, Gerard Waeber, Dawn M Waterworth, Xin Yuan, Leif Groop, Marju Orho-Melander, Wellcome Trust Case Control Consortium

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

997 Citations (Scopus)

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)	666-76
Number of pages	11
Journal	Nature Genetics
Volume	41
Issue number	6
DOIs	https://doi.org/10.1038/ng.361
Publication status	Published - 2009

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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., Khaw, K-T., ... Wellcome Trust Case Control Consortium (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics, 41(6), 666-76. https://doi.org/10.1038/ng.361

@article{da6ab13a52a349a184cd7dab51ab9008,

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 = "Christopher Newton-Cheh and Toby Johnson and Vesela Gateva and Tobin, {Martin D} and Murielle Bochud and Lachlan Coin and Najjar, {Samer S} and Zhao, {Jing Hua} and Heath, {Simon C} and Susana Eyheramendy and Konstantinos Papadakis and Voight, {Benjamin F} and Scott, {Laura J} and Feng Zhang and Martin Farrall and Toshiko Tanaka and Chris Wallace and Chambers, {John C} and Kay-Tee Khaw and Peter Nilsson and {van der Harst}, Pim and Silvia Polidoro and Grobbee, {Diederick E} and Onland-Moret, {N Charlotte} and Bots, {Michiel L} and Wain, {Louise V} and Elliott, {Katherine S} and Alexander Teumer and Jian'an Luan and Gavin Lucas and Johanna Kuusisto and Burton, {Paul R} and David Hadley and McArdle, {Wendy L} and Morris Brown and Anna Dominiczak and Newhouse, {Stephen J} and Samani, {Nilesh J} and John Webster and Eleftheria Zeggini and Beckmann, {Jacques S} and Sven Bergmann and Noha Lim and Kijoung Song and Peter Vollenweider and Gerard Waeber and Waterworth, {Dawn M} and Xin Yuan and Leif Groop and Marju Orho-Melander and {Wellcome Trust Case Control Consortium}",

year = "2009",

doi = "10.1038/ng.361",

language = "English",

volume = "41",

pages = "666--76",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Springer Nature",

number = "6",

}

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, K-T, 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, Groop, L, Orho-Melander, M & Wellcome Trust Case Control Consortium 2009, 'Genome-wide association study identifies eight loci associated with blood pressure', Nature Genetics, vol. 41, no. 6, pp. 666-76. https://doi.org/10.1038/ng.361

TY - JOUR

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

AU - Newton-Cheh, Christopher

AU - Johnson, Toby

AU - Gateva, Vesela

AU - Tobin, Martin D

AU - Bochud, Murielle

AU - Coin, Lachlan

AU - Najjar, Samer S

AU - Zhao, Jing Hua

AU - Heath, Simon C

AU - Eyheramendy, Susana

AU - Papadakis, Konstantinos

AU - Voight, Benjamin F

AU - Scott, Laura J

AU - Zhang, Feng

AU - Farrall, Martin

AU - Tanaka, Toshiko

AU - Wallace, Chris

AU - Chambers, John C

AU - Khaw, Kay-Tee

AU - Nilsson, Peter

AU - van der Harst, Pim

AU - Polidoro, Silvia

AU - Grobbee, Diederick E

AU - Onland-Moret, N Charlotte

AU - Bots, Michiel L

AU - Wain, Louise V

AU - Elliott, Katherine S

AU - Teumer, Alexander

AU - Luan, Jian'an

AU - Lucas, Gavin

AU - Kuusisto, Johanna

AU - Burton, Paul R

AU - Hadley, David

AU - McArdle, Wendy L

AU - Brown, Morris

AU - Dominiczak, Anna

AU - Newhouse, Stephen J

AU - Samani, Nilesh J

AU - Webster, John

AU - Zeggini, Eleftheria

AU - Beckmann, Jacques S

AU - Bergmann, Sven

AU - Lim, Noha

AU - Song, Kijoung

AU - Vollenweider, Peter

AU - Waeber, Gerard

AU - Waterworth, Dawn M

AU - Yuan, Xin

AU - Groop, Leif

AU - Orho-Melander, Marju

AU - Wellcome Trust Case Control Consortium

PY - 2009

Y1 - 2009

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.361

DO - 10.1038/ng.361

M3 - Article (Academic Journal)

C2 - 19430483

SN - 1061-4036

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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