Eight blood pressure loci identified by genome-wide association study of 34,433 people of European ancestry

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 2.5m genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,4...

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Detalles Bibliográficos
Autores principales: Newton-Cheh, Christopher, Johnson, Toby, Gateva, Vesela, Tobin, Martin D, Bochud, Murielle, Coin, Lachlan, Najjar, Samer S, Zhao, Jing Hua, Heath, Simon C, Eyheramendy, Susana, Papadakis, Konstantinos, Voight, Benjamin F, Scott, Laura J, Zhang, Feng, Farrall, Martin, Tanaka, Toshiko, Wallace, Chris, Chambers, John C, Khaw, Kay-Tee, Nilsson, Peter, van der Harst, Pim, Polidoro, Silvia, Grobbee, Diederick E, Onland-Moret, N Charlotte, Bots, Michiel L, Wain, Louise V, Elliott, Katherine S, Teumer, Alexander, Luan, Jian’an, Lucas, Gavin, Kuusisto, Johanna, Burton, Paul R, Hadley, David, McArdle, Wendy L, Brown, Morris, Dominiczak, Anna, Newhouse, Stephen J, Samani, Nilesh J, Webster, John, Zeggini, Eleftheria, Beckmann, Jacques S, Bergmann, Sven, Lim, Noha, Song, Kijoung, Vollenweider, Peter, Waeber, Gerard, Waterworth, Dawn M, Yuan, Xin, Groop, Leif, Orho-Melander, Marju, Allione, Alessandra, Di Gregorio, Alessandra, Guarrera, Simonetta, Panico, Salvatore, Ricceri, Fulvio, Romanazzi, Valeria, Sacerdote, Carlotta, Vineis, Paolo, Barroso, Inês, Sandhu, Manjinder S, Luben, Robert N, Crawford, Gabriel J., Jousilahti, Pekka, Perola, Markus, Boehnke, Michael, Bonnycastle, Lori L, Collins, Francis S, Jackson, Anne U, Mohlke, Karen L, Stringham, Heather M, Valle, Timo T, Willer, Cristen J, Bergman, Richard N, Morken, Mario A, Döring, Angela, Gieger, Christian, Illig, Thomas, Meitinger, Thomas, Org, Elin, Pfeufer, Arne, Wichmann, H Erich, Kathiresan, Sekar, Marrugat, Jaume, O’Donnell, Christopher J, Schwartz, Stephen M, Siscovick, David S, Subirana, Isaac, Freimer, Nelson B, Hartikainen, Anna-Liisa, McCarthy, Mark I, O’Reilly, Paul F, Peltonen, Leena, Pouta, Anneli, de Jong, Paul E, Snieder, Harold, van Gilst, Wiek H, Clarke, Robert, Goel, Anuj, Hamsten, Anders, Peden, John F, Seedorf, Udo, Syvänen, Ann-Christine, Tognoni, Giovanni, Lakatta, Edward G, Sanna, Serena, Scheet, Paul, Schlessinger, David, Scuteri, Angelo, Dörr, Marcus, Ernst, Florian, Felix, Stephan B, Homuth, Georg, Lorbeer, Roberto, Reffelmann, Thorsten, Rettig, Rainer, Völker, Uwe, Galan, Pilar, Gut, Ivo G, Hercberg, Serge, Lathrop, G Mark, Zeleneka, Diana, Deloukas, Panos, Soranzo, Nicole, Williams, Frances M, Zhai, Guangju, Salomaa, Veikko, Laakso, Markku, Elosua, Roberto, Forouhi, Nita G, Völzke, Henry, Uiterwaal, Cuno S, van der Schouw, Yvonne T, Numans, Mattijs E, Matullo, Giuseppe, Navis, Gerjan, Berglund, Göran, Bingham, Sheila A, Kooner, Jaspal S, Paterson, Andrew D, Connell, John M, Bandinelli, Stefania, Ferrucci, Luigi, Watkins, Hugh, Spector, Tim D, Tuomilehto, Jaakko, Altshuler, David, Strachan, David P, Laan, Maris, Meneton, Pierre, Wareham, Nicholas J, Uda, Manuela, Jarvelin, Marjo-Riitta, Mooser, Vincent, Melander, Olle, Loos, Ruth JF, Elliott, Paul, Abecasis, Goncalo R, Caulfield, Mark, Munroe, Patricia B
Formato: Texto
Lenguaje:English
Publicado: 2009
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2891673/
https://www.ncbi.nlm.nih.gov/pubmed/19430483
http://dx.doi.org/10.1038/ng.361
Descripción
Sumario: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 2.5m 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 8 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.

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