title: Lack of aggregation of ischemic stroke subtypes within affected sibling pairs.
abstract: OBJECTIVE
  To establish whether subtypes of ischemic stroke aggregate within ischemic stroke-affected sibling pairs more than expected by chance alone.
  
  
  METHODS
  This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umeå, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria.
  
  
  RESULTS
  Agreement for subtype diagnoses within families was poor (mean +/- asymptotic SE kappa = 0.17 +/- 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same-sex sibling pairs (kappa = 0.22 +/- 0.05) to sibling pairs in which the proband's stroke occurred before the age of 65 years (kappa = 0.16 +/- 0.05) or to pairs in which the proband's stroke occurred at or after the age of 65 years (kappa = 0.19 +/- 0.05).
  
  
  CONCLUSIONS
  The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype.
authors.affiliation: Department of Medicine, Umeå University, Umeå, Sweden.
authors.forename: P G
authors.initials: PG
authors.lastname: Wiklund
authors.forename: W M
authors.initials: WM
authors.lastname: Brown
authors.forename: T G
authors.initials: TG
authors.lastname: Brott
authors.forename: B
authors.initials: B
authors.lastname: Stegmayr
authors.forename: R D
authors.initials: RD
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Nilsson-Ardnor
authors.forename: J A
authors.initials: JA
authors.lastname: Hardy
authors.forename: B M
authors.initials: BM
authors.lastname: Kissela
authors.forename: A
authors.initials: A
authors.lastname: Singleton
authors.forename: D
authors.initials: D
authors.lastname: Holmberg
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
authors.forename: J F
authors.initials: JF
authors.lastname: Meschia
mesh_terms: D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000145:classification / Q000453:epidemiology* / Q000235:genetics*; D016000:Cluster Analysis; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D035781:Siblings; D020521:Stroke / Q000145:classification / Q000453:epidemiology* / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology