TY - JOUR
T1 - Genetic epidemiology of spontaneous subarachnoid hemorrhage
T2 - Nordic twin study
AU - Korja, Miikka
AU - Silventoinen, Karri
AU - McCarron, Peter
AU - Zdravkovic, Slobodan
AU - Skytthe, Axel
AU - Haapanen, Arto
AU - De Faire, Ulf
AU - Pedersen, Nancy L.
AU - Christensen, Kaare
AU - Koskenvuo, Markku
AU - Kaprio, Jaakko
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - familial
KW - genetics
KW - intracranial aneurysm
KW - SAH
KW - twin
UR - http://www.scopus.com/inward/record.url?scp=78149358125&partnerID=8YFLogxK
U2 - 10.1161/STROKEAHA.110.586420
DO - 10.1161/STROKEAHA.110.586420
M3 - Article
VL - 41
SP - 2458
EP - 2462
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 11
ER -