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, John M. Connell, Wellcome Trust Case Control Consor

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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 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 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 languageEnglish
    Pages (from-to)666-676
    Number of pages11
    JournalNature Genetics
    Volume41
    Issue number6
    DOIs
    Publication statusPublished - 2009

    Keywords

    • METHYLENETETRAHYDROFOLATE REDUCTASE GENE
    • LOW-RENIN HYPERTENSION
    • COMMON VARIANTS
    • CELL-DIFFERENTIATION
    • BARTTERS-SYNDROME
    • PUBLIC-HEALTH
    • RISK
    • POLYMORPHISM
    • POPULATION
    • MUTATIONS

    Cite this

    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 Consor (2009). Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics, 41(6), 666-676. https://doi.org/10.1038/ng.361