Abstract TMP30: Genetic Variants on 9p21.3 are Associated with Brain Arteriovenous Malformations with Associated Arterial Aneurysms

Abstract

Background: The 9p21.3 locus is associated with risk of coronary artery disease and intracranial and abdominal aortic aneurysms (rs10757278). We investigated whether previously reported 9p21.3 SNPs are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying flow-related arterial aneurysms. Methods: Genotypes for 6 SNPs, including rs10757278, were imputed using 1000 Genomes Phase 1 CEU data (R2>0.9). We tested for association using logistic regression of imputed dosages adjusting for age, sex and top 3 components of ancestry in 338 BAVM cases vs. 504 controls. Of these, 205 cases had aneurysm data available for subgroup analysis: (a) 74 BAVM+(with) aneurysm cases vs. 504 controls, and (b) 131 BAVM-(without) aneurysm cases vs. 504 controls. Results: rs10757278-G was marginally associated with increased risk of BAVM (OR=1.23, 95% CI=0.99-1.53, P=0.064). Compared to controls, the association was stronger in BAVM+aneurysm (OR=1.52, 95% CI=1.03-2.22, P=0.032) than in BAVM-aneurysm cases (OR=0.98, 95% CI=0.72-1.34, P=0.91). Similar effects were observed for other SNPs in linkage disequilibrium (r2>0.8) with rs10757278 (Table). Conclusion: Common 9p21.3 variants showed similar effect sizes as previously reported for aneurysmal disease. The SNP association with BAVM appears to be explained by known association with aneurysms, suggesting that BAVM associated aneurysms share similar vascular pathology mechanisms.