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)

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 <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 × 10⁻²⁴), 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• 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: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 10 May 2009

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Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
39252	1	Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular disease	Eleanor Davies	Medical Research Council (MRC)	G0400874	Institute of Cardiovascular and Medical Sciences
39252	2	Regulation of aldosterone and cortisol synthesis in hypertension and cardiovascular disease	Eleanor Davies	Medical Research Council (MRC)	G0400874	Institute of Cardiovascular and Medical Sciences