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Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.

Publication ,  Journal Article
Dungan, JR; Qin, X; Gregory, SG; Cooper-Dehoff, R; Duarte, JD; Qin, H; Gulati, M; Taylor, JY; Pepine, CJ; Hauser, ER; Kraus, WE
Published in: Am Heart J Plus
May 2022

BACKGROUND: Ischemic coronary heart disease (IHD) is the leading cause of death worldwide. Genetic variation is presumed to be a major factor underlying sex differences for IHD events, including mortality. The purpose of this study was to identify sex-specific candidate genes associated with all-cause mortality among people diagnosed with coronary artery disease (CAD). METHODS: We performed a sex-stratified, exploratory genome-wide association (GWAS) screen using existing data from CAD-diagnosed males (n = 510) and females (n = 174) who reported European ancestry from the Duke Catheterization Genetics biorepository. Extant genotype data for 785,945 autosomal SNPs generated with the Human Omni1-Quad BeadChip (Illumina, CA, USA) were analyzed using an additive inheritance model. We estimated instantaneous risk of all-cause mortality by genotype groups across the 11-year follow-up using Cox multivariate regression, covarying for age and genomic ancestry. RESULTS: The top GWAS hits associated with all-cause mortality among people with CAD included 8 SNPs among males and 15 among females (p = 1 × 10-6 or 10-7), adjusted for covariates. Cross-sex comparisons revealed distinct candidate genes. Biologically relevant candidates included rs9932462 (EMP2/TEKT5) and rs2835913 (KCNJ6) among males and rs7217169 (RAP1GAP2), rs8021816 (PRKD1), rs8133010 (PDE9A), and rs12145981 (LPGAT1) among females. CONCLUSIONS: We report 20 sex-specific candidate genes having suggestive association with all-cause mortality among CAD-diagnosed subjects. Findings demonstrate proof of principle for identifying sex-associated genetic factors that may help explain differential mortality risk in people with CAD. Replication and meta-analyses in larger studies with more diverse samples will strengthen future work in this area.

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Published In

Am Heart J Plus

DOI

EISSN

2666-6022

Publication Date

May 2022

Volume

17

Location

United States
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dungan, J. R., Qin, X., Gregory, S. G., Cooper-Dehoff, R., Duarte, J. D., Qin, H., … Kraus, W. E. (2022). Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease. Am Heart J Plus, 17. https://doi.org/10.1016/j.ahjo.2022.100152
Dungan, Jennifer R., Xue Qin, Simon G. Gregory, Rhonda Cooper-Dehoff, Julio D. Duarte, Huaizhen Qin, Martha Gulati, et al. “Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.Am Heart J Plus 17 (May 2022). https://doi.org/10.1016/j.ahjo.2022.100152.
Dungan JR, Qin X, Gregory SG, Cooper-Dehoff R, Duarte JD, Qin H, et al. Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease. Am Heart J Plus. 2022 May;17.
Dungan, Jennifer R., et al. “Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease.Am Heart J Plus, vol. 17, May 2022. Pubmed, doi:10.1016/j.ahjo.2022.100152.
Dungan JR, Qin X, Gregory SG, Cooper-Dehoff R, Duarte JD, Qin H, Gulati M, Taylor JY, Pepine CJ, Hauser ER, Kraus WE. Sex-dimorphic gene effects on survival outcomes in people with coronary artery disease. Am Heart J Plus. 2022 May;17.

Published In

Am Heart J Plus

DOI

EISSN

2666-6022

Publication Date

May 2022

Volume

17

Location

United States