A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls...

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Detalles Bibliográficos
Autores principales: Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M, Willenborg, Christina, Kanoni, Stavroula, Saleheen, Danish, Kyriakou, Theodosios, Nelson, Christopher P, Hopewell, Jemma C, Webb, Thomas R, Zeng, Lingyao, Dehghan, Abbas, Alver, Maris, Armasu, Sebastian M, Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I, Chen, Shufeng, Ford, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Hwang, Shih-Jen, Kim, Yun Kyoung, Kleber, Marcus E, Lau, King Wai, Lu, Xiangfeng, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mihailov, Evelin, Morrison, Alanna C, Pervjakova, Natalia, Qu, Liming, Rose, Lynda M, Salfati, Elias, Saxena, Richa, Scholz, Markus, Smith, Albert V, Tikkanen, Emmi, Uitterlinden, Andre, Yang, Xueli, Zhang, Weihua, Zhao, Wei, de Andrade, Mariza, de Vries, Paul S, van Zuydam, Natalie R, Anand, Sonia S, Bertram, Lars, Beutner, Frank, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H, Gottesman, Omri, Haber, Marc, Han, Bok-Ghee, Huang, Jianfeng, Jalilzadeh, Shapour, Kessler, Thorsten, König, Inke R, Lannfelt, Lars, Lieb, Wolfgang, Lind, Lars, Lindgren, Cecilia M, Lokki, Marja-Liisa, Magnusson, Patrik K, Mallick, Nadeem H, Mehra, Narinder, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P, Nieminen, Markku S, Pedersen, Nancy L, Peters, Annette, Rallidis, Loukianos S, Rasheed, Asif, Samuel, Maria, Shah, Svati H, Sinisalo, Juha, Stirrups, Kathleen E, Trompet, Stella, Wang, Laiyuan, Zaman, Khan S, Ardissino, Diego, Boerwinkle, Eric, Borecki, Ingrid B, Bottinger, Erwin P, Buring, Julie E, Chambers, John C, Collins, Rory, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Elosua, Roberto, Epstein, Stephen E, Esko, Tõnu, Feitosa, Mary F, Franco, Oscar H, Franzosi, Maria Grazia, Granger, Christopher B, Gu, Dongfeng, Gudnason, Vilmundur, Hall, Alistair S, Hamsten, Anders, Harris, Tamara B, Hazen, Stanley L, Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J, Kim, Bong-Jo, Kooner, Jaspal S, Kullo, Iftikhar J, Lehtimäki, Terho, Loos, Ruth J F, Melander, Olle, Metspalu, Andres, März, Winfried, Palmer, Colin N, Perola, Markus, Quertermous, Thomas, Rader, Daniel J, Ridker, Paul M, Ripatti, Samuli, Roberts, Robert, Salomaa, Veikko, Sanghera, Dharambir K, Schwartz, Stephen M, Seedorf, Udo, Stewart, Alexandre F, Stott, David J, Thiery, Joachim, Zalloua, Pierre A, O’Donnell, Christopher J, Reilly, Muredach P, Assimes, Themistocles L, Thompson, John R, Erdmann, Jeanette, Clarke, Robert, Watkins, Hugh, Kathiresan, Sekar, McPherson, Ruth, Deloukas, Panos, Schunkert, Heribert, Samani, Nilesh J, Farrall, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589895/
https://www.ncbi.nlm.nih.gov/pubmed/26343387
http://dx.doi.org/10.1038/ng.3396
Descripción
Sumario:Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

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