Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk

he risk of intracranial aneurysm (IA) is increased among individuals with first-degree relatives with history of IA. 1 Many approaches have been used to identify genes contributing to the risk of IA. 2–4 Genome-wide association studies identified and replicated associations on chromosome 4q31. Most studies utilized sporadic IA cases; familial cases may potentially involve different genetic risk factors. The present study was undertaken to compare and contrast results from a genome-wide association study of familial and sporadic IA cases. Discovery sample (DS) 1 consisted of individuals recruited through the Familial Intracranial Aneurysm (FIA) I study, 7 which recruited familial cases appropriate for linkage analysis 8 through an international consortium and applied rigorous inclusion and exclusion criteria. A set of independent unrelated cases was obtained by Background—Genome-wide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. Method—We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a meta-analysis. Results—There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genome-wide significance. However, the meta-analysis yielded genome-wide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6×10