{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:42Z","timestamp":1747185162518,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,2]],"date-time":"2023-08-02T00:00:00Z","timestamp":1690934400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The etiology of non\u2010syndromic biliary atresia (BA) remains largely unknown. In this study, we performed genome\u2010wide screening of genes associated with the risk of non\u2010syndromic BA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed exome data of 15 Japanese patients with non\u2010syndromic BA and 509 control individuals using an optimal sequence kernel association test (SKAT\u2010O), a gene\u2010based association study optimized for small\u2010number subjects. Furthermore, we examined the frequencies of known BA\u2010related single\u2010nucleotide polymorphisms in the BA and control groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SKAT\u2010O showed that rare damaging variants of <jats:italic>MFHAS1<\/jats:italic>, a ubiquitously expressed gene encoding a Toll\u2010like receptor\u2010associated protein, were more common in the BA group than in the control group (Bonferroni corrected <jats:italic>p<\/jats:italic>\u2010value\u00a0=\u00a00.0097). Specifically, p.Val106Gly and p.Arg556Cys significantly accumulated in the patient group. These variants resided within functionally important domains. SKAT\u2010O excluded the presence of other genes significantly associated with the disease risk. Of 60 known BA\u2010associated single\u2010nucleotide polymorphisms, only eight were identified in the BA group. In particular, p.Ile3421Met of <jats:italic>MYO15A<\/jats:italic> and p.Ala421Thr of <jats:italic>THOC2<\/jats:italic> were more common in the BA group than in the control group. However, the significance of these two variants is questionable, because <jats:italic>MYO15A<\/jats:italic> has been linked to deafness, but not to BA, and the p.Ala421Thr of <jats:italic>THOC2<\/jats:italic> represents a relatively common single\u2010nucleotide polymorphism in Asia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of this study indicate that rare damaging variants in <jats:italic>MFHAS1<\/jats:italic> may constitute a risk factor for non\u2010syndromic BA, whereas the contribution of other monogenic variants to the disease predisposition is limited.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13946","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T05:01:02Z","timestamp":1690347662000},"page":"1134-1141","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Rare sequence variants associated with the risk of non\u2010syndromic 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