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Title:

A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.

Document type:
Journal Article; Meta-Analysis; Article
Author(s):
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,...     »
Abstract:
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.
Journal title abbreviation:
Nat Genet
Year:
2015
Journal volume:
47
Journal issue:
10
Pages contribution:
1121-30
Language:
eng
Fulltext / DOI:
doi:10.1038/ng.3396
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/26343387
Print-ISSN:
1061-4036
TUM Institution:
Institut für Humangenetik; Klinik für Herz- und Kreislauferkrankungen im Erwachsenenalter (Prof. Schunkert)
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