rs10757274
badMag 6.5This is a intergenic variant variant in the CDKN2B-AS1 gene.
Key Literature Trait Associations
Coronary Artery Disease
Located in the 9p21 locus near CDKN2A/B, the strongest and most replicated common genetic risk factor for coronary artery disease. The risk allele is very common, affecting ~47% of the population. The locus regulates cell proliferation in vascular smooth muscle.
Abdominal aortic aneurysm
The A allele of rs10757274 is significantly associated with abdominal aortic aneurysm (AAA). A large GWAS meta-analysis (GWAS Catalog GCST003877; ~4,972 cases / 99,858 controls, predominantly European ancestry) identified this variant at p=2×10⁻³³ with OR=1.24 (95% CI 1.20–1.29). A 2021 systematic review of AAA GWAS studies confirmed the CDKN2B-AS1/9p21 locus as showing the strongest AAA association overall, with rs10757274 achieving p=1.54×10⁻³³. The 9p21.3 association with AAA appears largely independent of its CAD association, suggesting shared but partially distinct vascular biology.
Angina pectoris
The G allele at rs10757274 is strongly associated with angina pectoris across large population-based studies. GWAS Catalog records from UK Biobank-derived analyses report beta=0.153–0.158 log-odds with p-values as low as 2×10⁻⁸¹, reflecting very high statistical confidence in this association (risk allele frequency ~0.47–0.47). This is consistent with the broader 9p21.3 atherosclerosis signal, where angina likely reflects the same underlying coronary disease risk pathway mediated through CDKN2B-AS1 regulation of vascular cell growth and senescence.
Sudden cardiac death
The G allele at rs10757274 is associated with increased risk of sudden and arrhythmic cardiac death. A 2009 prospective study within the Women's Health Study (492 sudden cardiac deaths, 1,460 matched controls) found that each additional G allele conferred an adjusted OR of 1.29 (95% CI 1.09–1.53, P=0.003) for sudden cardiac death. Notably, this association was partly independent of the variant's CAD risk effect, suggesting additional mechanisms beyond atherosclerosis—possibly related to arrhythmia susceptibility or cardiac remodeling regulated by the CDKN2B-AS1/ANRIL locus.
Ischemic stroke
Multiple meta-analyses of ANRIL polymorphisms have identified rs10757274 as a modest but significant risk factor for ischemic stroke (IS). A 2022 comprehensive meta-analysis (25 studies; up to 11,527 cases / 12,216 controls) found significant association with IS, particularly in Caucasians, with the strongest signal in the large artery atherosclerosis subtype. A 2019 meta-analysis (18 studies) reported OR=0.91 for the allele model (P=0.006), and a meta-analysis in Chinese populations (9,756 individuals) found OR=1.09 (95% CI 1.01–1.17, P=0.03). The association is modest and may be driven by shared atherosclerotic mechanisms with CAD, with greater effect in Asian subgroups.
▶GWAS Catalog Trait Associations (6)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (6)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
▶Research that mentions this SNP (1)
▶Common genetic polymorphisms in Moyamoya and atherosclerotic disease in EuropeansAssociationN=108Constantin Roder et al.(2011)· Child's Nervous System
Case-control study of 40 European Moyamoya disease patients versus 68 controls found a significant association between rs599839 (A/G, OR=2.17, 95% CI=1.17-4.05, p=0.01) in the PSRC1 gene and Moyamoya disease, along with three additional SNPs showing borderline significance in ELN and CXCL12 genes. The findings suggest shared genetic pathways between Moyamoya disease and atherosclerotic disease.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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