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A comprehensive 1000 genomes–based genome-wide association meta-analysis of coronary artery disease.
Nat. Genet. 47, 1121-1130 (2015)
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 casual 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.
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Publication type
Article: Journal article
Document type
Scientific Article
Language
english
Publication Year
2015
HGF-reported in Year
2015
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Journal
Nature Genetics
Quellenangaben
Volume: 47,
Issue: 10,
Pages: 1121-1130
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504091-004
G-504000-001
G-500700-001
G-504100-001
G-501900-402
G-504000-001
G-500700-001
G-504100-001
G-501900-402
DOI
10.1038/ng.3396
WOS ID
WOS:000361969900007
Scopus ID
84942987885
Scopus ID
84940932825
Erfassungsdatum
2015-10-07