{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:37:26Z","timestamp":1758587846310,"version":"3.44.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["2021R1C1C1005725"],"award-info":[{"award-number":["2021R1C1C1005725"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>East Asia has one of the highest global stroke burdens. Genetically, moyamoya disease (MMD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) contribute to this burden. This study investigated the allele frequencies and estimated the genetic prevalence of <jats:italic>RNF213<\/jats:italic> and <jats:italic>NOTCH3<\/jats:italic> variants in a large Korean population.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Between July 2021 and August 2024, 129,933 individuals who underwent health checkups were included. <jats:italic>RNF213<\/jats:italic> p.Arg4810Lys and three <jats:italic>NOTCH3<\/jats:italic> variants, p.Arg544Cys, p.Arg640Cys, and p.Arg75Pro, were analyzed using next-generation sequencing. Allele frequencies were calculated, and genetic prevalence was estimated using the Hardy-Weinberg equilibrium.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>The allele frequency of <jats:italic>RNF213<\/jats:italic> p.Arg4810Lys was 1.08%, with 13 homozygotes. The estimated genetic prevalence of MMD was 1 in 47 individuals. For <jats:italic>NOTCH3<\/jats:italic>, the allele frequencies were 0.07% for p.Arg544Cys, 0.07% for p.Arg640Cys, and 0.04% for p.Arg75Pro, corresponding to an estimated genetic prevalence of CADASIL of 1 in 277 individuals. Eight individuals carried both the <jats:italic>RNF213<\/jats:italic> and <jats:italic>NOTCH3<\/jats:italic> variants.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This large-scale study highlights the substantial genetic burden of <jats:italic>RNF213<\/jats:italic> and <jats:italic>NOTCH3<\/jats:italic> variants in Koreans, which partially contributes to the high stroke burden in East Asia. These findings emphasize the importance of population-specific genetic studies to optimize cerebrovascular disorder management in East Asia.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0331174","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T17:27:42Z","timestamp":1758562062000},"page":"e0331174","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic epidemiology of moyamoya disease and CADASIL in over 120,000 healthy Korean individuals: Insights into cerebrovascular disorders"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9328-9389","authenticated-orcid":true,"given":"Eun Hye","family":"Cho","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoungkeun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Seok","family":"Ki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang Ahn","family":"Seol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-5236","authenticated-orcid":true,"given":"Mi-Ae","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"issue":"10","key":"pone.0331174.ref001","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S1474-4422(24)00369-7","article-title":"Global, regional, and national burden of stroke and its risk factors, 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