초록/요약

Background and Purpose: Genetic factors have been known to play a role in the etiology of moyamoya disease (MMD); however, population-level studies quantifying familial risk estimates are unavailable. We aimed to quantify familial incidence and risk for MMD in first-degree relatives (FDR) in the general population of Korea. Methods: By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21 940 795 study subjects constituting 12 million families with blood-related FDR and followed them for a familial occurrence of MMD from 2002 to 2017. Incidence risk ratios were calculated as MMD incidence in individuals with affected FDR compared with those without affected FDR, according to age, sex, and family relationships. Results: Among total study subjects, there were 22 459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8/10(4)person-years. Overall, the familial risk for MMD was 132-fold higher in individuals with versus without affected FDR. Familial risk (incidence risk ratio; incidence/10(4)person-years) increased with the degree of genetic relatedness, being highest in individuals with an affected twin (1254.1; 230.0), followed by a sibling (212.4; 35.6), then mother (87.7; 14.4) and father (62.5; 10.4). Remarkably, there was no disease concordance between spouses. The risks were age-dependent and were particularly high in younger age groups. Familial risks were similar in males and females, and the risk of disease transmission was higher in same-sex parent-offspring and sibling pairs. Conclusions: Our study indicates that genetic predisposition is the predominant driver in MMD pathogenesis, with minimal contribution of environmental factors. These results could be utilized to direct future genetic studies and clinical risk counseling.