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

• DOI: 10.1161/strokeaha.112.656397
• Publication Date: 2012-09-08T00:30:23Z
• Authors: Tatiana Foroud; Daniel L. Koller; Dongbing Lai; Laura Sauerbeck; Craig Anderson; Nerissa Ko; Ranjan Deka; Thomas H. Mosley; Myriam Fornage; Daniel Woo; Charles J. Moomaw; Richard Hornung; John Huston; Irene Meissner; Joan E. BaileyWilson; Carl Langefeld; Guy Rouleau; E. Sander Connolly; Bradford B. Worrall; Dawn Kleindorfer; Matthew L. Flaherty; Sharyl Martini; Jason Mackey; Felipe De Los Rio...; Robert D. Brown; Joseph P. Broderick
• Keywords: SNP; Genome-wide Association Study; Genetic Association; Imputation (statistics); Multiple comparisons problem

Background— Genomewide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought confirm previously reported loci, identify risk factors, and evaluate the contribution of these familial sporadic IA. Method— utilized 2 complementary samples, one recruited on basis a dense family history IA (discovery sample 1: 388 cases 397 controls) other without regard 2: 1095 1286 controls). Imputation was used generate common set single nucleotide polymorphisms (SNP) across logistic regression model test for in each sample. Results from were then combined metaanalysis. Results— There only modest overlap results obtained samples. In neither did reach genomewide significance. However, metaanalysis yielded significance SNP chromosome 9p ( CDKN2BAS ; rs6475606; P =3.6 × 10 −8 ) provided further evidence support with SOX17 8q (rs1072737; =8.7 −5 ). Analyses suggest effect smoking acts multiplicatively genotype, has greater than genotype. Conclusion— addition replicating several we provide is attributable variants (also known as ANRIL , an antisense noncoding RNA).