Genetic epidemiology of spontaneous subarachnoid hemorrhage

Nordic twin study

Miikka Korja*, Karri Silventoinen, Peter McCarron, Slobodan Zdravkovic, Axel Skytthe, Arto Haapanen, Ulf De Faire, Nancy L. Pedersen, Kaare Christensen, Markku Koskenvuo, Jaakko Kaprio

*Corresponding author for this work

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    Background and Purpose: 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.

    Original languageEnglish
    Pages (from-to)2458-2462
    Number of pages5
    JournalStroke
    Volume41
    Issue number11
    DOIs
    Publication statusPublished - Nov 2010

    Keywords

    • familial
    • genetics
    • intracranial aneurysm
    • SAH
    • twin

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