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CARDIoGRAMplusC4D Consortium (Nikpay, M.* ; Goel, A.* ; Won, H.* ; Hall, L.M.* ; Willenborg, C.* ; Kanoni, S.* ; Saleheen, D.* ; Gieger, C. ; Meitinger, T. ; Peters, A. ; Watkins, H.* ; Kathiresan, S.* ; MacPherson, R.*)

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

Nat. Genet. 47, 1121-1130 (2015)
Supplement Research data DOI
Open Access Green as soon as Postprint is submitted to ZB.
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 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
POF-Topic(s) 30202 - Environmental Health
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
Scopus ID 84942987885
Scopus ID 84940932825
Erfassungsdatum 2015-10-07