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

Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Martin Farrall and colleagues report the results of a large genome-wide association meta-analysis of coronary artery disease based on 1000 Genomes imputation. They identify ten new risk loci and show that susceptibility to this disease is largely deter...

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Published in:	Nature genetics Vol. 47; no. 10; pp. 1121 - 1130
Main Authors:	Nikpay, Majid, Goel, Anuj, Won, Hong-Hee, Hall, Leanne M, Willenborg, Christina, Kanoni, Stavroula, Kyriakou, Theodosios, Nelson, Christopher P, Harris, Tamara B, Hazen, Stanley L, Hengstenberg, Christian, Hofman, Albert, Ingelsson, Erik, Iribarren, Carlos, Jukema, J Wouter, Karhunen, Pekka J, Kim, Bong-Jo, Webb, Thomas R, Kullo, Iftikhar J, Loos, Ruth JF, Melander, Olle, Metspalu, Andres, Palmer, Colin N, Quertermous, Thomas, Rader, Daniel J, Zeng, Lingyao, Ridker, Paul M, Roberts, Robert, Schwartz, Stephen M, Stewart, Alexandre F, Stott, David J, Thiery, Joachim, Dehghan, Abbas, Zalloua, Pierre A, O'Donnell, Christopher J, Thompson, John R, Erdmann, Jeanette, Clarke, Robert, Kathiresan, Sekar, McPherson, Ruth, Alver, Maris, Deloukas, Panos, Samani, Nilesh J, Farrall, Martin, Auro, Kirsi, Bjonnes, Andrew, Chasman, Daniel I, Chen, Shufeng, d, Ian, Franceschini, Nora, Gieger, Christian, Grace, Christopher, Gustafsson, Stefan, Huang, Jie, Kim, Yun Kyoung, Lau, King Wai, Lyytikäinen, Leo-Pekka, Morrison, Alanna C, Pervjakova, Natalia, Rose, Lynda M, Salfati, Elias, Saxena, Richa, Scholz, Markus, Tikkanen, Emmi, Uitterlinden, Andre, Zhang, Weihua, de Andrade, Mariza, van Zuydam, Natalie R, Dedoussis, George, Frossard, Philippe, Gauguier, Dominique, Goodall, Alison H, Gottesman, Omri, Haber, Marc, Huang, Jianfeng, König, Inke R, Lannfelt, Lars, Lind, Lars, Lindgren, Cecilia M, Magnusson, Patrik K, Mallick, Nadeem H, Meitinger, Thomas, Memon, Fazal-ur-Rehman, Morris, Andrew P, Nieminen, Markku S, Rallidis, Loukianos S, Rasheed, Asif, Sinisalo, Juha, Stirrups, Kathleen E, Wang, Laiyuan, Ardissino, Diego, Boerwinkle, Eric, Bottinger, Erwin P, Buring, Julie E, Chambers, John C, Cupples, L Adrienne, Danesh, John, Demuth, Ilja, Gudnason, Roberto, Hamsten, Anders
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.10.2015 Nature Publishing Group
Subjects:	45/43 631/208/205/2138 692/699/75/2/1674 Agriculture Analysis Animal Genetics and Genomics Basic Medicine Biomedicine Cancer Research Cardiology and Cardiovascular Disease Cardiovascular disease Cardiovascular research Clinical Medicine Coronary heart disease Coronary vessels Development and progression Gene Function Gene loci Genetic aspects Genetic research Genetic susceptibility Genetic variance Genomes Haplotypes Health aspects Heart attacks Heterogeneity Human Genetics Kardiologi och kardiovaskulära sjukdomar Klinisk medicin Medical and Health Sciences Medical Genetics and Genomics (including Gene Therapy) Medicin och hälsovetenskap Medicinsk genetik och genomik (Här ingår: Genterapi) Medicinska och farmaceutiska grundvetenskaper Meta-analysis Ratios Single nucleotide polymorphisms Vein & artery diseases
ISSN:	1061-4036, 1546-1718, 1546-1718
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Summary:	Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Martin Farrall and colleagues report the results of a large genome-wide association meta-analysis of coronary artery disease based on 1000 Genomes imputation. They identify ten new risk loci and show that susceptibility to this disease is largely determined by common SNPs with small effect sizes. Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus 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.
Bibliography:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 These authors jointly supervised this work.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.3396