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

• Published in: Nature genetics Vol. 41; no. 6; pp. 666 - 676
• Main Authors: Newton-Cheh, Christopher, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Coin, Lachlan, Zhao, Jing Hua, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, van der Harst, Pim, Polidoro, Silvia, Elliott, Katherine S, Teumer, Alexander, Luan, Jian'an, Kuusisto, Johanna, Hadley, David, McArdle, Wendy L, Dominiczak, Anna, Samani, Nilesh J, Webster, John, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J, Jousilahti, Pekka, Perola, Markus, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Stringham, Heather M, Valle, Timo T, Bergman, Richard N, Gieger, Christian, Illig, Thomas, Kathiresan, Sekar, O'Donnell, Christopher J, Subirana, Isaac, Freimer, Nelson B, O'Reilly, Paul F, Peltonen, Leena, Pouta, Anneli, de Jong, Paul E, Snieder, Harold, van Gilst, Wiek H, Clarke, Robert, Hamsten, Anders, Peden, John F, Seedorf, Udo, Lakatta, Edward G, Sanna, Serena, Scuteri, Angelo, Dörr, Marcus, Ernst, Florian, Felix, Stephan B, Homuth, Georg, Gut, Ivo G, Lathrop, G Mark, Zelenika, Diana, Deloukas, Panos, Soranzo, Nicole, Williams, Frances M, Salomaa, Veikko, Laakso, Markku, Elosua, Roberto, Forouhi, Nita G, Völzke, Henry, Uiterwaal, Cuno S, van der Schouw, Yvonne T, Matullo, Giuseppe, Navis, Gerjan, Berglund, Göran, Kooner, Jaspal S, Bandinelli, Stefania, Watkins, Hugh, Tuomilehto, Jaakko, Altshuler, David, Laan, Maris, Meneton, Pierre, Jarvelin, Marjo-Riitta, Mooser, Vincent, Melander, Olle, Elliott, Paul, Caulfield, Mark, Munroe, Patricia B
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2009; Nature Publishing Group
• Subjects: Adaptor Proteins, Signal Transducing; Agriculture; Animal Genetics and Genomics; Annan klinisk medicin; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood pressure; Blood Pressure - genetics; Cancer Research; Cardiac and Cardiovascular Systems; Cardiology and Cardiovascular Disease; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - genetics; Cardiovascular Diseases - physiopathology; Chromosome Mapping; Clinical Medicine; Cytochrome P-450 CYP1A2 - genetics; Data analysis; Diastole - genetics; DNA-Binding Proteins - genetics; Endocrinology and Diabetes; Endokrinologi och diabetes; Europe; Fibroblast Growth Factor 5 - genetics; Fundamental and applied biological sciences. Psychology; Gene Function; Gene loci; Genetic aspects; Genetic variance; Genetic Variation; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomics; Human Genetics; Humans; Hypertension; India; Intracellular Signaling Peptides and Proteins; Kardiologi; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; Medical and Health Sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Meta-analysis; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Open Reading Frames - genetics; Other Clinical Medicine; Phospholipase C delta - genetics; Physiological aspects; Polymorphism, Single Nucleotide; Proteins - genetics; Risk factors; Single nucleotide polymorphisms; Statistics; Steroid 17-alpha-Hydroxylase - genetics; Studies; Systole - genetics; White People - genetics; Europe; India; United Kingdom; Identification; Blood pressure; Association; Hemodynamics; Locus
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.361

Christopher Newton-Cheh and colleagues report a genome-wide association study for blood pressure traits as part of the Global BPgen consortium. They report eight loci with replicated association to systolic and/or diastolic blood pressure, with each also showing association to hypertension. 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.