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

Author(s): 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, L. Groop, M. Orho-Melander, A. Allione, A. Di Gregorio, S. Guarrera, S. Panico, F. Ricceri, V. Romanazzi, C. Sacerdote, P. Vineis, I. Barroso, M. S. Sandhu, R. N. Luben, G. J. Crawford, P. Jousilahti, M. Perola, M. Boehnke, L. L. Bonnycastle, F. S. Collins, A. U. Jackson, K. L. Mohlke, H. M. Stringham, T. T. Valle, C. J. Willer, R. N. Bergman, M. A. Morken, A. Doring, C. Gieger, T. Illig, T. Meitinger, E. Org, A. Pfeufer, H. E. Wichmann, S. Kathiresan, J. Marrugat, C. J. O'Donnell, S. M. Schwartz, D. S. Siscovick, I. Subirana, N. B. Freimer, A. L. Hartikainen, M. I. McCarthy, P. F. O'Reilly, L. Peltonen, A. Pouta, P. E. de Jong, H. Snieder, W. H. van Gilst, R. Clarke, A. Goel, A. Hamsten, J. F. Peden, U. Seedorf, A. C. Syvanen, G. Tognoni, E. G. Lakatta, S. Sanna, P. Scheet, D. Schlessinger, A. Scuteri, M. Dorr, F. Ernst, S. B. Felix, G. Homuth, R. Lorbeer, T. Reffelmann, R. Rettig, U. Volker, P. Galan, I. G. Gut, S. Hercberg, G. M. Lathrop, D. Zelenika, P. Deloukas, N. Soranzo, F. M. Williams, G. Zhai, V. Salomaa, M. Laakso, R. Elosua, N. G. Forouhi, H. Volzke, C. S. Uiterwaal, Y. T. van der Schouw, M. E. Numans, G. Matullo, G. Navis, G. Berglund, S. A. Bingham, J. S. Kooner, J. M. Connell, S. Bandinelli, L. Ferrucci, H. Watkins, T. D. Spector, J. Tuomilehto, D. Altshuler, D. P. Strachan, M. Laan, P. Meneton, N. J. Wareham, M. Uda, M. R. Jarvelin, V. Mooser, O. Melander, R. J. F. Loos, P. Elliott, G. R. Abecasis, M. Caulfield, P. B. Munroe, Consor Wellcome Trust Case Control

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.

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ISBN: 1061-4036
Publication Year: 2009
Periodical: Nature Genetics
Periodical Number: 6
Volume: 41
Pages: 666-676
Author Address: