title: Search for intracranial aneurysm susceptibility gene(s) using Finnish families.
abstract: BACKGROUND
  Cerebrovascular disease is the third leading cause of death in the United States, and about one-fourth of cerebrovascular deaths are attributed to ruptured intracranial aneurysms (IA). Epidemiological evidence suggests that IAs cluster in families, and are therefore probably genetic. Identification of individuals at risk for developing IAs by genetic tests will allow concentration of diagnostic imaging on high-risk individuals. We used model-free linkage analysis based on allele sharing with a two-stage design for a genome-wide scan to identify chromosomal regions that may harbor IA loci.
  
  
  METHODS
  We previously estimated sibling relative risk in the Finnish population at between 9 and 16, and proceeded with a genome-wide scan for loci predisposing to IA. In 85 Finnish families with two or more affected members, 48 affected sibling pairs (ASPs) were available for our genetic study. Power calculations indicated that 48 ASPs were adequate to identify chromosomal regions likely to harbor predisposing genes and that a liberal stage I lod score threshold of 0.8 provided a reasonable balance between detection of false positive regions and failure to detect real loci with moderate effect.
  
  
  RESULTS
  Seven chromosomal regions exceeded the stage I lod score threshold of 0.8 and five exceeded 1.0. The most significant region, on chromosome 19q, had a maximum multipoint lod score (MLS) of 2.6.
  
  
  CONCLUSIONS
  Our study provides evidence for the locations of genes predisposing to IA. Further studies are necessary to elucidate the genes and their role in the pathophysiology of IA, and to design genetic tests.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA. olson@darwin.epbi.cwru.edu
authors.forename: Jane M
authors.initials: JM
authors.lastname: Olson
authors.forename: Sompong
authors.initials: S
authors.lastname: Vongpunsawad
authors.forename: Helena
authors.initials: H
authors.lastname: Kuivaniemi
authors.forename: Antti
authors.initials: A
authors.lastname: Ronkainen
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Markku
authors.initials: M
authors.lastname: Ryynänen
authors.forename: Lee-Lian
authors.initials: LL
authors.lastname: Kim
authors.forename: Gerard
authors.initials: G
authors.lastname: Tromp