Key result
Sex-specific genetic variants, including rs1432687863 in males, were associated with coronary artery disease risk in an Iranian cohort.
Why the study?
Coronary artery disease is influenced by sex and genetics, but previous GWAS have mostly evaluated European populations, leaving sex-related genetic differences in the Iranian population uncharacterized.
Does the genetic architecture of coronary artery disease differ by sex in an Iranian population?
Cohort (n=5,441)
Does the genetic architecture of coronary artery disease differ by sex in an Iranian population?
A sex-stratified genome-wide association study in an Iranian cohort identified novel sex-specific genetic variants associated with coronary artery disease, highlighting the importance of sex-specific genetic analyses.
Sex-specific CAD SNPs should not yet inform risk models; leaves open their added value beyond standard factors in diverse ancestries.
BACKGROUND: The development of coronary artery disease (CAD) is influenced by sex and genetic factors. Genome-wide association studies (GWAS) have linked genetic loci to CAD, mostly in European populations. The study aims to find sex-related genetic differences in the Iranian population. RESEARCH DESIGN AND METHODS: We conducted a sex-stratified GWAS with 4519 subjects (1832 males and 2687 females) in the discovery group and 922 subjects (495 males and 427 females) in the confirmation group of an Iranian cohort. We analyzed 9,141,124 variants using a genome-wide complex trait analysis (GCTA) tool. RESULTS: = 7.142-8E] positively influenced CAD risk. The CAD-associated SNPs that were obtained have been confirmed using independent samples. Rs3495229 May impact histone mark and Pou2f2 motifs, while rs7314741 in the LEM Domain Containing 3 (LEMD3) promoter may affect a regulatory motif for the STAT transcription factor. According to Roadmap and ENCODE data, Rs1432687863 is a new variant affecting CAD in males, potentially through H3K9me3 in the heart. CONCLUSIONS: Our findings highlight the role of sex-specific genetic differences in CAD development, providing novel insights into disease pathways which is not appropriate using a sex-combined strategy. [Figure: see text].
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Bonab et al. (2024) conducted a cohort in coronary artery disease (CAD) (n=5,441). Sex-specific genetic variants was evaluated on Coronary artery disease risk. Sex-specific genetic variants, including rs1432687863 in males, were associated with coronary artery disease risk in an Iranian cohort.
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