Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease

Musameh, Muntaser D., Wang, William Y. S., Nelson, Christopher P., Lluis-Ganella, Carla, Debiec, Radoslaw, Subirana, Isaac, Elosua, Roberto, Balmforth, Anthony J., Ball, Stephen G., Hall, Alistair S., Kathiresan, Sekar, Thompson, John R., Lucas, Gavin, Samani, Nilesh J. and Tomaszewski, Maciej (2015) Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease. PLoS One, 10 2: . doi:10.1371/journal.pone.0117684

Author Musameh, Muntaser D.
Wang, William Y. S.
Nelson, Christopher P.
Lluis-Ganella, Carla
Debiec, Radoslaw
Subirana, Isaac
Elosua, Roberto
Balmforth, Anthony J.
Ball, Stephen G.
Hall, Alistair S.
Kathiresan, Sekar
Thompson, John R.
Lucas, Gavin
Samani, Nilesh J.
Tomaszewski, Maciej
Title Analysis of gene-gene interactions among common variants in candidate cardiovascular genes in coronary artery disease
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-02-06
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pone.0117684
Open Access Status DOI
Volume 10
Issue 2
Total pages 12
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2015
Language eng
Formatted abstract
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.

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
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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