title: Familial effects on ischemic stroke: the role of sibling kinship, sex, and age of onset.
abstract: BACKGROUND
  Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence.
  
  
  RESULTS
  Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48-1.75; P<0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50-1.81; P<0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10-1.82; P=0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41-2.67; P<0.001).
  
  
  CONCLUSIONS
  There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kasiman
authors.forename: Cecilia
authors.initials: C
authors.lastname: Lundholm
authors.forename: Sven
authors.initials: S
authors.lastname: Sandin
authors.forename: Ninoa
authors.initials: N
authors.lastname: Malki
authors.forename: Pär
authors.initials: P
authors.lastname: Sparén
authors.forename: Erik
authors.initials: E
authors.lastname: Ingelsson
mesh_terms: D017668:Age of Onset; D000368:Aged; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012307:Risk Factors; D012737:Sex Factors; D035781:Siblings; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D013548:Sweden / Q000453:epidemiology