title: Genome-wide association study of intracranial aneurysms confirms role of Anril and SOX17 in disease risk.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Indiana University School of Medicine, 410 W. 10 Street, Indianapolis, IN 46202, USA. tforoud@iupui.edu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Dongbing
authors.initials: D
authors.lastname: Lai
authors.forename: Laura
authors.initials: L
authors.lastname: Sauerbeck
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.forename: Nerissa
authors.initials: N
authors.lastname: Ko
authors.forename: Ranjan
authors.initials: R
authors.lastname: Deka
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Moomaw
authors.forename: Richard
authors.initials: R
authors.lastname: Hornung
authors.forename: John
authors.initials: J
authors.lastname: Huston
authors.forename: Irene
authors.initials: I
authors.lastname: Meissner
authors.forename: Joan E
authors.initials: JE
authors.lastname: Bailey-Wilson
authors.forename: Carl
authors.initials: C
authors.lastname: Langefeld
authors.forename: Guy
authors.initials: G
authors.lastname: Rouleau
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Worrall
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Flaherty
authors.forename: Sharyl
authors.initials: S
authors.lastname: Martini
authors.forename: Jason
authors.initials: J
authors.lastname: Mackey
authors.forename: Felipe
authors.initials: F
authors.lastname: De Los Rios La Rosa
authors.forename: Robert D
authors.initials: RD
authors.lastname: Brown
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding / Q000235:genetics*; D012307:Risk Factors; D055760:SOXF Transcription Factors / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors