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Introduction: Sporadic brain arteriovenous malformations (BAVMs) are rare vascular lesions that are a major cause of intracerebral hemorrhage (ICH) in younger persons. Genetic risk factors for ICH in BAVM have not been firmly established. Late-onset primary ICH is more common, with several candidate loci reported. It is not known whether genetic variants associated with primary ICH are also associated with BAVM ICH.Methods: We performed a case-control study including 138 Caucasian cases with BAVM ICH and 504 healthy Caucasian controls. We tested 8 candidate variants reported for primary ICH in or near 7 genes (ACE, APOE, COL4A2, MTHFR, PMF1, SLC25A44, and TRHDE). Genotypes were extracted from existing Affymetrix genome-wide array data or from PCR-based assays for 3 variants. Logistic regression was used to determine whether candidate variants (or, when unavailable, proxy variants in high linkage disequilibrium) were associated with BAVM ICH, assuming an additive genetic model and adjusting for age and sex. We considered variants statistically significant if P<0.05 and in the same direction of association (risk allele) as reported for primary ICH.Results: No statistically significant associations were observed between BAVM ICH and genetic variants implicated in primary ICH. The strongest finding was for rs9521733 in COL4A2 (OR=1.26, P=0.13). Further evaluation of the COL4A2 +/- 5kb locus revealed nine variants associated with BAVM ICH; the strongest association was with rs9521692 (OR=0.49, P=0.001).Conclusions: Specific candidate variants implicated in primary ICH were not significantly associated with BAVM ICH, suggesting that genetic risk factors may differ between primary and BAVM ICH. The COL4A2 locus may contain additional variants associated with BAVM ICH but will require larger studies to validate findings.