{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:54:07Z","timestamp":1789199647612,"version":"build-2803163510"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>By using the Korean National Health Insurance database which has complete population coverage and confirmed FDR information, we constructed a cohort of 21\u2009940\u2009795 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Among total study subjects, there were 22\u2009459 individuals with affected FDR, of whom 712 familial cases developed MMD with an incidence of 21.8\/10\n              <jats:sup>4<\/jats:sup>\n              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\n              <jats:sup>4<\/jats:sup>\n              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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.120.029251","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T18:01:31Z","timestamp":1598292091000},"page":"2752-2760","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Familial Risk for Moyamoya Disease Among First-Degree Relatives, Based on a Population-Based Aggregation Study in Korea"],"prefix":"10.1161","volume":"51","author":[{"given":"Hyeong Sik","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Preventive Medicine, College of Medicine (H.S.A., S.Z.K., H.J.K.), Korea University, Seoul."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-3637","authenticated-orcid":true,"given":"Sayada Zartasha","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, College of Medicine (H.S.A., S.Z.K., H.J.K.), Korea University, Seoul."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1467-2281","authenticated-orcid":true,"given":"Taeuk","family":"Kang","sequence":"additional","affiliation":[{"name":"Korean Research-based Pharma Industry Association (KRPIA), Seoul, Korea (T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2372-1807","authenticated-orcid":true,"given":"Dong-Sook","family":"Kim","sequence":"additional","affiliation":[{"name":"Health Insurance Review and Assessment Service (HIRA), Wonju, Korea (D.S.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-7586","authenticated-orcid":true,"given":"Taekyun","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Public Health (T.R.), Korea University, Seoul."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-6763","authenticated-orcid":true,"given":"Jae Sang","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Soonchunhyang University, Cheonan Hospital, Korea (J.S.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-1520","authenticated-orcid":true,"given":"Hoo Jae","family":"Hann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2018-2385","authenticated-orcid":true,"given":"Hyun Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, College of Medicine (H.S.A., S.Z.K., H.J.K.), Korea University, Seoul."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"288","article-title":"Cerebrovascular \u201cMoyamoya\u201d disease: disease showing abnormal net-like vessels in base of brain.","volume":"20","author":"Suzuki J","year":"1969","unstructured":"Suzuki, J, Takaku, A. Cerebrovascular \u201cMoyamoya\u201d disease: disease showing abnormal net-like vessels in base of brain. JAMA Neurology. 1969;20;288\u2013299.","journal-title":"JAMA Neurology"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804622"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.01627"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.004273"},{"key":"e_1_3_4_6_2","first-page":"1977","article-title":"Epidemiology, diagnosis and treatment of Moyamoya disease.","volume":"17","author":"Zhang H","year":"2019","unstructured":"Zhang, H, Zheng, L, Feng, L. Epidemiology, diagnosis and treatment of Moyamoya disease. Exp Ther Med. 2019;17;1977\u20131984.","journal-title":"Exp Ther Med"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000176066.33797.82"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1789.2000.00300.x"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2015.01760"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0143-6"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/302243"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/088307380001500307"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.4.930"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.132"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1007\/s00381-006-0089-4","article-title":"Familial occurrence of Moyamoya disease: a clinical study.","volume":"22","author":"Seol HJ","year":"2006","unstructured":"Seol, HJ, Wang, K-C, Kim, S-K, Hwang, Y-S, Kim, KJ, Cho, B-K. Familial occurrence of Moyamoya disease: a clinical study. Childs Nerv Syst. 2006;22;1143\u20131148.","journal-title":"Childs Nerv Syst"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2006.096040"},{"key":"e_1_3_4_17_2","first-page":"1227","article-title":"A genetic study of spontaneous occlusion of the circle of Willis (Moyamoya disease).","volume":"62","author":"Kanai N","year":"1992","unstructured":"Kanai, N. A genetic study of spontaneous occlusion of the circle of Willis (Moyamoya disease). Tokyo Joshi Ikadaigaku Zasshi. 1992;62;1227\u20131258.","journal-title":"Tokyo Joshi Ikadaigaku Zasshi"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.42.3.208"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0303-8467(97)00054-1"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1007\/s00381-005-1230-5","article-title":"Clinical features of familial Moyamoya disease.","volume":"22","author":"Nanba R","year":"2006","unstructured":"Nanba, R, Kuroda, S, Tada, M, Ishikawa, T, Houkin, K, Iwasaki, Y. Clinical features of familial Moyamoya disease. Childs Nerv Syst. 2006;22;258\u2013262.","journal-title":"Childs Nerv Syst"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023972"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2176\/nmc.38.349","article-title":"Familial occurrence of Moyamoya disease in the mother and four daughters including identical twins - case report.","volume":"38","author":"Kaneko Y","year":"1998","unstructured":"Kaneko, Y, Imamoto, N, Mannoji, H, Fukui, M. Familial occurrence of Moyamoya disease in the mother and four daughters including identical twins - case report. Neurol Med Chir (Tokyo). 1998;38:349\u2013354.","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0887-8994(00)00215-0"},{"key":"e_1_3_4_24_2","first-page":"6","article-title":"Direction of policy and management for rare intractable disease patients support program.","volume":"3","author":"Yeom MS","year":"2009","unstructured":"Yeom, MS. Direction of policy and management for rare intractable disease patients support program. Health Insurance Review & Assessment Service (HIRA) Policy Review. 2009;3:6\u201310.","journal-title":"Health Insurance Review & Assessment Service (HIRA) Policy Review"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-004-1005-4"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.3171\/jns.1983.59.6.1092","article-title":"Moyamoya syndrome in only one of two identical twins.","volume":"59","author":"Tanghe\u2019iti B","year":"1983","unstructured":"Tanghe\u2019iti, B, Capra, R, Giunta, F, Marini, G, Orlandini, A. Moyamoya syndrome in only one of two identical twins. J Neurosurg. 1983;59;1092\u20131094.","journal-title":"J Neurosurg"},{"key":"e_1_3_4_27_2","first-page":"142","article-title":"Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis.","volume":"100","author":"Scott RM","year":"2004","unstructured":"Scott, RM, Smith, JL, Robertson, RL, Madsen, JR, Soriano, SG, Rockoff, MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg. 2004;100;142\u2013149.","journal-title":"J Neurosurg"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/01902140490495606","article-title":"Familial risk for lung cancer by histology and age of onset: evidence for recessive inheritance.","volume":"31","author":"Hemminki K","year":"2005","unstructured":"Hemminki, K, Li, X. Familial risk for lung cancer by histology and age of onset: evidence for recessive inheritance. Exp Lung Res. 2005;31;205\u2013215.","journal-title":"Exp Lung Res"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.2000.1585"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291012.49986.f9"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2014.16.2.65"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022542"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048179"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.114.006244"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318249f71f"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3171\/2015.4.JNS142900"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0378-1119(01)00721-1","article-title":"Epigenetics: interaction of DNA methylation and chromatin.","volume":"278","author":"Nakao M","year":"2001","unstructured":"Nakao, M. Epigenetics: interaction of DNA methylation and chromatin. Gene. 2001;278:25\u201331.","journal-title":"Gene"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.481"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088765"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.120.029251","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T15:32:47Z","timestamp":1715614367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.120.029251"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1161\/STROKEAHA.120.029251"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.120.029251","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"2020-01-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}