title: Genetic epidemiology of spontaneous subarachnoid hemorrhage: Nordic Twin Study.
abstract: OBJECTIVE
  It would be essential to clinicians, familial aneurysm study groups, and aneurysm families to understand the genetic basis of subarachnoid hemorrhage (SAH), but there are no large population-based heritability estimates assessing the relative contribution of genetic and environmental factors to SAH.
  
  
  METHODS
  We constructed the largest twin cohort to date, the population-based Nordic Twin Cohort, which comprised 79 644 complete twin pairs of Danish, Finnish, and Swedish origin. The Nordic Twin Cohort was followed up for 6.01 million person-years using nationwide cause-of-death and hospitalization registries.
  
  
  RESULTS
  One hundred eighty-eight fatal and 321 nonfatal SAH cases were recorded in the Nordic Twin Cohort. Thus, SAH incidence was 8.47 cases per 100,000 follow-up years. Data for pairwise analyses were available for a total of 504 SAH cases, of which 6 were concordant (5 monozygotic and 1 opposite sex) and 492 discordant twin pairs for SAH. The concordance for SAH in monozygotic twins was 3.1% compared with 0.27% in dizygotic twins, suggesting at most a modest role for genetic factors in the etiology of SAH. The population-based probability estimate for SAH in dizygotic siblings of a patient with SAH is 0.54%, and only 1 of 185 full siblings experience familial SAH. The corresponding risk of SAH in monozygotic twins is 5.9%. Model-fitting, which was based on the comparison of the few monozygotic and dizygotic pairs, suggested that the estimated heritability of SAH is 41%.
  
  
  CONCLUSIONS
  SAH appears to be mainly of nongenetic origin, and familial SAHs can mostly be attributed to environmental risk factors.
authors.affiliation: Department of Neurosurgery, Helsinki University Central Hospital, Finland. miikka.korja@hus.fi
authors.forename: Miikka
authors.initials: M
authors.lastname: Korja
authors.forename: Karri
authors.initials: K
authors.lastname: Silventoinen
authors.forename: Peter
authors.initials: P
authors.lastname: McCarron
authors.forename: Slobodan
authors.initials: S
authors.lastname: Zdravkovic
authors.forename: Axel
authors.initials: A
authors.lastname: Skytthe
authors.forename: Arto
authors.initials: A
authors.lastname: Haapanen
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Markku
authors.initials: M
authors.lastname: Koskenvuo
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000208:ethnology / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012042:Registries; D012907:Smoking / Q000208:ethnology / Q000235:genetics; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D014429:Twins, Dizygotic / Q000208:ethnology / Q000235:genetics; D014430:Twins, Monozygotic / Q000208:ethnology / Q000235:genetics; D055815:Young Adult