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

Newton-Cheh, C. et al. (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nature Genetics, 41(6), pp. 666-676. (doi: 10.1038/ng.361)

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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 <i>in silico</i> 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<sup>−24</sup>), CYP1A2 (P = 1 × 10<sup>−23</sup>), FGF5 (P = 1 × 10<sup>−21</sup>), SH2B3 (P = 3 × 10<sup>−18</sup>), MTHFR (P = 2 × 10<sup>−13</sup>), c10orf107 (P = 1 × 10<sup>−9</sup>), ZNF652(P = 5 × 10<sup>−9</sup>) and PLCD3 (P = 1 × 10<sup>−8</sup>) 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Dominiczak, Professor Anna
Authors: 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., Nilsson, P., van der Harst, P., Polidoro, S., Grobbee, D. E., Onland-Moret, N. C., Bots, M. L., Wain, L. V., Elliott, K. S., Teumer, A., Luan, J.'a., Lucas, G., Kuusisto, J., Burton, P. R., Hadley, D., McArdle, W. L., Brown, M., Dominiczak, A., Newhouse, S. J., Samani, N. J., Webster, J., Zeggini, E., Beckmann, J. S., Bergmann, S., Lim, N., Song, K., Vollenweider, P., Waeber, G., Waterworth, D. M., 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, M. S., Luben, R. N., Crawford, G. J., Jousilahti, P., Perola, M., Boehnke, M., Bonnycastle, L. L., Collins, F. S., Jackson, A. U., Mohlke, K. L., Stringham, H. M., Valle, T. T., Willer, C. J., Bergman, R. N., Morken, M. A., Döring, A., Gieger, C., Illig, T., Meitinger, T., Org, E., Pfeufer, A., Wichmann, H. E., Kathiresan, S., Marrugat, J., O'Donnell, C. J., Schwartz, S. M., Siscovick, D. S., Subirana, I., Freimer, N. B., Hartikainen, A.-L., McCarthy, M. I., O'Reilly, P. F., Peltonen, L., Pouta, A., de Jong, P. E., Snieder, H., Wiek H., v. G., Robert, C., Goel, A., Hamsten, A., Peden, J. F., Seedorf, U., Syvänen, A.-C., Tognoni, G., Lakatta, E. G., Sanna, S., Scheet, P., Schlessinger, D., Scuteri, A., Dörr, M., Ernst, F., Felix, S. B., Homuth, G., Lorbeer, R., Reffelmann, T., Rettig, R., Völker, U., Galan, P., Gut, I. G., Hercberg, S., Lathrop, G. M., Zelenika, D., Deloukas, P., Soranzo, N., Williams, F. M., Zhai, G., Salomaa, V., Laakso, M., Elosua, R., Forouhi, N. G., Völzke, H., Uiterwaal, C. S., van der Schouw, Y. T., Numans, M. E., Matullo, G., Navis, G., Berglund, G., Bingham, S. A., Kooner, J. S., Connell, J. M., Bandinelli, S., Ferrucci, L., Watkins, H., Spector, T. D., Tuomilehto, J., Altshuler, D., Strachan, D. P., Laan, M., Meneton, P., Wareham, N. J., Uda, M., Jarvelin, M.-R., Mooser, V., Melander, O., Loos, R. J. F., Elliott, P., Abecasis, G. R., Caulfield, M., and Munroe, P. B.
College/School:College of Medical Veterinary and Life Sciences
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN (Online):1546-1718
Published Online:10 May 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
392521Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences
392522Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular diseaseEleanor DaviesMedical Research Council (MRC)G0400874Institute of Cardiovascular and Medical Sciences