TY - JOUR
T1 - Genome-wide association study of intracranial aneurysms confirms role of anril and SOX17 in disease risk
AU - Foroud, Tatiana
AU - Koller, Daniel L.
AU - Lai, Dongbing
AU - Sauerbeck, Laura
AU - Anderson, Craig
AU - Ko, Nerissa
AU - Deka, Ranjan
AU - Mosley, Thomas H.
AU - Fornage, Myriam
AU - Woo, Daniel
AU - Moomaw, Charles J.
AU - Hornung, Richard
AU - Huston, John
AU - Meissner, Irene
AU - Baileywilson, Joan E.
AU - Langefeld, Carl
AU - Rouleau, Guy
AU - Sander Connolly, E.
AU - Worrall, Bradford B.
AU - Kleindorfer, Dawn
AU - Flaherty, Matthew L.
AU - Martini, Sharyl
AU - Mackey, Jason
AU - De Los Rios La Rosa, Felipe
AU - Brown, Robert D.
AU - Broderick, Joseph P.
PY - 2012/11
Y1 - 2012/11
N2 - Background-Genomewide 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 metaanalysis. RESULTS-: There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6 × 10) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7 × 10). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. Conclusion-In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).
AB - Background-Genomewide 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 metaanalysis. RESULTS-: There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6 × 10) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7 × 10). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. Conclusion-In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).
KW - genome-wide association study
KW - intracranial aneurysm
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U2 - 10.1161/STROKEAHA.112.656397
DO - 10.1161/STROKEAHA.112.656397
M3 - Article
C2 - 22961961
AN - SCOPUS:84868192579
SN - 0039-2499
VL - 43
SP - 2846
EP - 2852
JO - Stroke
JF - Stroke
IS - 11
ER -