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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
Broad Inst MIT & Harvard Univ, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA USA..
Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
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2015 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 10, 1121-1130 p.Article in journal (Refereed) Published
Abstract [en]

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 similar to 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.

Place, publisher, year, edition, pages
2015. Vol. 47, no 10, 1121-1130 p.
National Category
Medical Genetics Cardiac and Cardiovascular Systems
URN: urn:nbn:se:uu:diva-265694DOI: 10.1038/ng.3396ISI: 000361969900007OAI: oai:DiVA.org:uu-265694DiVA: diva2:867499
Swedish National Infrastructure for Computing (SNIC), b2011036
Available from: 2015-11-05 Created: 2015-11-02 Last updated: 2016-05-10Bibliographically approved

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Gustafsson, StefanLannfelt, LarsLind, LarsIngelsson, Erik
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