title: Genome screen in familial intracranial aneurysm.
abstract: BACKGROUND
  Individuals with 1st degree relatives harboring an intracranial aneurysm (IA) are at an increased risk of IA, suggesting genetic variation is an important risk factor.
  
  
  METHODS
  Families with multiple members having ruptured or unruptured IA were recruited and all available medical records and imaging data were reviewed to classify possible IA subjects as definite, probable or possible IA or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of IA reported to date. A 'narrow' (n = 705 definite IA cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene x smoking interaction.
  
  
  RESULTS
  Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene x smoking interaction was detected using both disease models on chromosome 7p (60 cM; p </= 0.01). Our study provides modest evidence of possible linkage to several chromosomes.
  
  
  CONCLUSIONS
  These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the IA families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA. tforoud@iupui.edu
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Laura
authors.initials: L
authors.lastname: Sauerbeck
authors.forename: Robert
authors.initials: R
authors.lastname: Brown
authors.forename: Craig
authors.initials: C
authors.lastname: Anderson
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Flaherty
authors.forename: Ranjan
authors.initials: R
authors.lastname: Deka
authors.forename: Richard
authors.initials: R
authors.lastname: Hornung
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: Dongbing
authors.initials: D
authors.lastname: Lai
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: John
authors.initials: J
authors.lastname: Huston
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D002532:Intracranial Aneurysm / Q000209:etiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects