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Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease.
J. Am. Coll. Cardiol. 69, 823-836 (2017)
Background Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. Objectives This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. Methods In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. Results We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10−4 with a range of other diseases/traits. Conclusions We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cholesteryl Ester Transfer Protein ; Expression Quantitative Trait Loci ; Genetics ; Genome-wide Association ; Single Nucleotide Polymorphism; Genome-wide Association; Density-lipoprotein Receptor; Abdominal Aortic-aneurysm; Heart-disease; Scavenger Receptor; Phospholipase A(2); Common Variants; Cetp Mass; Sr-bi; Risk
Language
english
Publication Year
2017
HGF-reported in Year
2017
ISSN (print) / ISBN
0735-1097
e-ISSN
1558-3597
Quellenangaben
Volume: 69,
Issue: 7,
Pages: 823-836
Publisher
Elsevier
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
POF-Topic(s)
30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-504000-006
G-504091-001
G-504100-001
G-500700-001
G-504091-001
G-504100-001
G-500700-001
PubMed ID
28209224
WOS ID
WOS:000396340400009
Scopus ID
85013005062
Erfassungsdatum
2017-03-07