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Title: Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease.
Authors: Musameh, Muntaser D.
Wang, W. Y.
Nelson, Christopher P.
Lluís-Ganella, C.
Debiec, Radoslaw
Subirana, I.
Elosua, R.
Balmforth, A. J.
Ball, S. G.
Hall, A. S.
Kathiresan, S.
Thompson, John R.
Lucas, G.
Samani, Nilesh Jayantilal
Tomaszewski, Maciej
First Published: 6-Feb-2015
Publisher: Public Library of Science
Citation: PLoS One, 2015, 10 (2), e0117684
Abstract: OBJECTIVE: Only a small fraction of coronary artery disease (CAD) heritability has been explained by common variants identified to date. Interactions between genes of importance to cardiovascular regulation may account for some of the missing heritability of CAD. This study aimed to investigate the role of gene-gene interactions in common variants in candidate cardiovascular genes in CAD. APPROACH AND RESULTS: 2,101 patients with CAD from the British Heart Foundation Family Heart Study and 2,426 CAD-free controls were included in the discovery cohort. All subjects were genotyped with the Illumina HumanCVD BeadChip enriched for genes and pathways relevant to the cardiovascular system and disease. The primary analysis in the discovery cohort examined pairwise interactions among 913 common (minor allele frequency >0.1) independent single nucleotide polymorphisms (SNPs) with at least nominal association with CAD in single locus analysis. A secondary exploratory interaction analysis was performed among all 11,332 independent common SNPs surviving quality control criteria. Replication analyses were conducted in 2,967 patients and 3,075 controls from the Myocardial Infarction Genetics Consortium. None of the interactions amongst 913 SNPs analysed in the primary analysis was statistically significant after correction for multiple testing (required P<1.2x10-7). Similarly, none of the pairwise gene-gene interactions in the secondary analysis reached statistical significance after correction for multiple testing (required P = 7.8x10-10). None of 36 suggestive interactions from the primary analysis or 31 interactions from the secondary analysis was significant in the replication cohort. Our study had 80% power to detect odds ratios > 1.7 for common variants in the primary analysis. CONCLUSIONS: Moderately large additive interactions between common SNPs in genes relevant to cardiovascular disease do not appear to play a major role in genetic predisposition to CAD. The role of genetic interactions amongst less common SNPs and with medium and small magnitude effects remain to be investigated.
DOI Link: 10.1371/journal.pone.0117684
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2015 Musameh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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