{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:07:50Z","timestamp":1787728070392,"version":"build-2784847793"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Ring finger protein 213<\/jats:italic> (<jats:italic>RNF213<\/jats:italic>) is a susceptibility gene of moyamoya disease (MMD). A previous case\u2013control study and a family analysis demonstrated a strong association of the East Asian\u2010specific variant, R4810K (rs112735431), with MMD. Our aim is to uncover evolutionary history of R4810K in East Asian populations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The <jats:italic>RNF213<\/jats:italic> locus of 24 MMD patients in Japan were sequenced using targeted\u2010capture sequencing. Based on the sequence data, we conducted population genetic analysis and estimated the age of R4810K using coalescent simulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The diversity of the <jats:italic>RNF213<\/jats:italic> gene was higher in Africans than non\u2010Africans, which can be explained by bottleneck effect of the out\u2010of\u2010Africa migration. Coalescent simulation showed that the risk variant was born in East Asia 14,500\u20135100 years ago and came to the Japanese archipelago afterward, probably in the period when the known migration based on archaeological evidences occurred.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although clinical data show that the symptoms varies, all sequences harboring the risk allele are almost identical with a small number of exceptions, suggesting the MMD phenotypes are unaffected by the variants of this gene and rather would be more affected by environmental factors.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12424","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T07:25:28Z","timestamp":1621495528000},"page":"166-177","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An analysis of the demographic history of the risk allele R4810K in <i>RNF213<\/i> of 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