Journal article
Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk
Stroke (1970), Vol.43(11), pp.2846-2852
2012
DOI: 10.1161/STROKEAHA.112.656397
PMCID: PMC3752852
PMID: 22961961
Abstract
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 × 10−8) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7 × 10−5). 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).
Details
- Title: Subtitle
- Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk
- Creators
- Tatiana FOROUD - Indiana University School of Medicine, Indianapolis, IN, United StatesDaniel L KOLLER - Indiana University School of Medicine, Indianapolis, IN, United StatesCharles J MOOMAW - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesRichard HORNUNG - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesJohn HUSTON - Mayo Clinic, Rochester, MN, United StatesIrene MEISSNER - Mayo Clinic, Rochester, MN, United StatesFamilial Intracranial Aneurysm (FIA) Study InvestigatorsCarl LANGEFELD - Wake Forest University, Winston-Salem, NC, United StatesGuy ROULEAU - University of Montreal, Montreal, Quebec, CanadaE. Sander CONNOLLY - Columbia University School of Medicine, New York, NY, United StatesBradford B WORRALL - University of Virginia School of Medicine, Charlottesville, United StatesDawn KLEINDORFER - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesDongbing Lai - Indiana University School of Medicine, Indianapolis, IN, United StatesMatthew L FLAHERTY - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesSharyl MARTINI - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesJason MACKEY - Indiana University School of Medicine, Indianapolis, IN, United StatesFelipe DE LOS RIOS LA ROSA - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesRobert D BROWN - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesJoseph P BRODERICK - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesLaura SAUERBECK - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesCraig ANDERSON - The George Institute for Global Health of Royal Prince Alfred Hospital and University of Sydney, Sydney, AustraliaNerissa KO - University of California, San Francisco, San Francisco, CA, United StatesRanjan DEKA - Mayo Clinic, Rochester, MN, United StatesThomas H MOSLEY - University of Mississippi Medical Center, Jackson, MS, United StatesMyriam FORNAGE - University of Texas Health Science Center, Houston, TX, United StatesDaniel WOO - University of Cincinnati College of Medicine, Cincinnati, OH, United StatesFIA Study Investigators
- Contributors
- Colin P Derdeyn (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.43(11), pp.2846-2852
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/STROKEAHA.112.656397
- PMID
- 22961961
- PMCID
- PMC3752852
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 2012
- Academic Unit
- Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984013110102771
Metrics
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