Key result
Six-variant genetic risk score linked to ~20% higher early-onset CAD risk per allele.
Why the study?
Evidence of genetic predisposition to CAD is derived mostly from European and East Asian populations, leaving risk factors in other groups unclear.
Do specific genetic variants and a genetic risk score increase the risk of early-onset coronary artery disease in an Iranian population?
Case-Control (n=1,608)
Do specific genetic variants and a genetic risk score increase the risk of early-onset coronary artery disease in an Iranian population?
Genetic risk factors, including variants previously linked to venous thrombosis, are associated with early-onset CAD in Iranians and substantially amplify risk when combined with metabolic comorbidities.
Answers are grounded in this paper and cite their sources.
Does not support clinical adoption; extends European/East Asian loci to Iranians while highlighting metabolic interactions.
Background: Coronary artery disease (CAD) is a leading cause of death worldwide. Evidence of genetic predisposition is derived mostly from studies of Europeans and East Asians. Objectives: To test selected variants for association with early-onset CAD. Methods: We performed a case-control study of 697 young angiography-defined CAD cases (women aged <55 years, men <45) and 911 age- and sex-matched controls in Iran. We tested 24 variants (12 established CAD loci, 12 candidates in hemostasis genes) using age- and sex-adjusted logistic regression, stratified by ethnicity. A 6-variant unweighted genetic risk score (GRS) was built from the top loci. Additive interaction with cardiovascular risk factors was assessed by relative excess risk due to interaction. Results: Of 12 established loci, HCG27–HLA-C, CDKN2A/CDKN2B, and SORT1 showed nominal or near-nominal replication and 4 were directionally aligned with prior literature, whereas 5 showed no association. Among hemostasis candidates, F5 rs4524 was nominally associated with increased risk, and TSPAN15 rs78707713 and F11 rs2289252 suggested reduced risk. Ethnicity-stratified analyses indicated nominal or suggestive ancestry-specific effects at SORT1, HCG27–HLA-C, CDKN2A/CDKN2B, LPA, VWF, MIA3, and CXCL12. The GRS (range, 2-11 alleles/person) yielded a per-allele odds ratio of 1.20 (95% CI, 1.12-1.29), ie, a 5.2-fold higher risk across the observed range. Combining GRS with metabolic comorbidities showed super-additive effects (relative excess risk due to interaction, 6.66; 95% CI, 2.04-11.28). Conclusion: Ten variants, including 3 previously linked to venous thrombosis, showed nominal or suggestive association with early-onset CAD in Iranians or specific ethnic groups. Genetic burden substantially amplified risk in the presence of metabolic comorbidities. Our findings underscore the need for ancestry-aware studies in multiethnic populations.
No takes yet. Share an insight, caveat, or question.
Mancini et al. (2026) conducted a case-control in Early-onset coronary artery disease (n=1,608). 6-variant genetic risk score (GRS) vs. Fewer risk alleles was evaluated on Early-onset coronary artery disease (OR 1.20, 95% CI 1.12-1.29). A 6-variant genetic risk score was associated with a per-allele odds ratio of 1.20 for early-onset coronary artery disease in Iranians, with risk substantially amplified by metabolic comorbidities.
Synapse has enriched 10 related papers. Consider them for comparative context: