Abstract
Introduction: Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis. CAC has been shown to strongly correlate with the amount of atherosclerotic plaque and predicts future coronary disease events and mortality. CAC is a complex heritable trait and levels differ by sex. We investigated the interaction between sex and genome wide association study (GWAS) signals on chromosome 6p24 and 9p21 on Coronary Artery Calcium (CAC) in the COPDGene study. Hypothesis: We assessed the hypothesis that sex would interact with the GWAS signals on CAC. Methods: The COPDGene is a study of 10,192 current and former smokers with at least 10 pack-years of smoking history. CAC was measured using high dose, inspiration chest CT scans, following an established protocol in 8,739 individuals (6,150 non-Hispanic Whites (NHW) and 2,589 African Americans (AA)). We considered sex by SNP interactions on CAC for our previously identified GWAS signals on chromosome 6p24 and chromosome 9p21 using R software adjusting for genetic ancestry using principal components as well as recognized risk factors (age, pack-years of smoking history, BMI, diabetes, high blood pressure, high cholesterol, and steroid use). We used the log transformation of CAC plus 1 as the quantitative phenotype. Results: There was a significant interaction between sex and chromosome 6p24 PHACTR1 [rs9349379] (p=0.023) on CAC among NHW subjects in the COPDGene study. There was a genome-wide significant association for rs9349379 with CAC among male NHW subjects [p-value= 1.21E-8] but not among female NHW subjects [p-value= 0.02]. Overall there was no genome-wide significant association for rs9349379 with CAC among all NHW subjects [p-value= 6.39E-7]. There was no significant interaction between sex and chromosome 9p21 CDKN2B-AS1 [rs10757272] (p-value=0.25) on CAC among NHW COPDGene subjects. Among AA subjects in the COPDGene study, there was not a significant interaction between sex and rs9349379 [ PHACTR1 ] (p-value=0.48) or sex and rs10757272 [ CDKN2B-AS1 ] (p-value=0.21) on CAC. Conclusions: There was a SNP by sex interaction on CAC for chromosome 6p24 with a genome wide significant signal for NHW men but not for NHW women. The chromosome 9p21 signal for CAC did not significantly differ by sex. This study demonstrates the importance of considering gene by sex interactions in genome wide association studies of cardiovascular disease risk.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
