{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:08:12Z","timestamp":1790348892275,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T00:00:00Z","timestamp":1684108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["21ZR1452600"],"award-info":[{"award-number":["21ZR1452600"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170527"],"award-info":[{"award-number":["82170527"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019988","name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition","doi-asserted-by":"publisher","award":["17DZ2272000"],"award-info":[{"award-number":["17DZ2272000"]}],"id":[{"id":"10.13039\/100019988","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The <jats:italic>Jagged1<\/jats:italic> (<jats:italic>JAG1<\/jats:italic>) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in <jats:italic>JAG1<\/jats:italic> with isolated BA risk in the Chinese Han population.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We genotyped 31 tag single nucleotide polymorphisms covering the <jats:italic>JAG1<\/jats:italic> gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of <jats:italic>JAG1<\/jats:italic> homologs were investigated in zebrafish embryos, and the roles of <jats:italic>jag1<\/jats:italic>a and <jats:italic>jag1b<\/jats:italic> in biliary development were examined by morpholino knockdown in zebrafish.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Single nucleotide polymorphisms rs6077861 [<jats:italic>P<\/jats:italic><jats:sub><jats:italic>Allelic<\/jats:italic><\/jats:sub> = 1.74 \u00d7 10<jats:sup>\u22124<\/jats:sup>, odds ratio = 1.78, 95% confidence interval: 1.31\u20132.40] and rs3748478 (<jats:italic>P<\/jats:italic><jats:sub><jats:italic>Allelic<\/jats:italic><\/jats:sub> = 5.77 \u00d7 10<jats:sup>\u22124<\/jats:sup>, odds ratio = 1.39, 95% confidence interval: 1.15\u20131.67) located in the intron region of <jats:italic>JAG1<\/jats:italic> showed significant associations with BA susceptibility. The <jats:italic>JAG1<\/jats:italic> homologs, <jats:italic>jag1a<\/jats:italic> and <jats:italic>jag1b<\/jats:italic> genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96\u00a0h postfertilization. Knockdown of both <jats:italic>jag1a<\/jats:italic> and <jats:italic>jag1b<\/jats:italic> led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Common genetic variants of <jats:italic>JAG1<\/jats:italic> were associated with BA susceptibility. Knockdown of <jats:italic>JAG1<\/jats:italic> homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that <jats:italic>JAG1<\/jats:italic> might be implicated in the etiology of BA.<\/jats:p>","DOI":"10.3389\/fgene.2023.1186882","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T05:07:27Z","timestamp":1684127247000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Association analysis and functional follow-up identified common variants of JAG1 accounting for risk to biliary atresia"],"prefix":"10.3389","volume":"14","author":[{"given":"Mei-Rong","family":"Bai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Yue","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Lei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hua","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ming","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Wen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Meng","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei-Lin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/nrgastro.2015.74","article-title":"Pathogenesis of biliary atresia: Defining biology to understand clinical phenotypes","volume":"12","author":"Asai","year":"2015","journal-title":"Nat. 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