{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T04:05:21Z","timestamp":1754107521990},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T00:00:00Z","timestamp":1431302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["WIREs Mechanisms of Disease"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Biliary atresia (<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>) is a model complex disease resulting from interactions between multiple susceptibility loci and environmental factors. This perception is based on a heterogeneous phenotype extending beyond an absent extrahepatic bile duct to include gut and cardiovascular anomalies, and the association of <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> with viral infections. Refractory jaundice and progression to cirrhosis shortly after birth can be fatal without surgical correction, and further suggests a pathogenesis during liver and bile duct development. Conclusive proof for a developmental origin would require documentation of disease progression in the perinatal or fetal liver, an impossible task for obvious reasons. We review three different sets of genome\u2010wide association studies (<jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content>) from three different cohorts of <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> patients by three different groups of investigators, which address this knowledge gap. Knockdown of each susceptibility gene identified by <jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content> in zebrafish embryos impairs excretion of bile from the liver, duplicating the characteristic diagnostic finding seen in affected children. This finding is associated with impaired intrahepatic biliary network formation in zebrafish morphants. Although distinct, these susceptibility genes share several functions including roles in mechanisms for organogenesis (glypican 1 or <jats:italic><jats:styled-content style=\"fixed-case\">GPC1<\/jats:styled-content>,<\/jats:italic> and adenosine diphosphate ribosylation factor 6, or <jats:italic><jats:styled-content style=\"fixed-case\">ARF6<\/jats:styled-content><\/jats:italic>) or a greater expression in fetal liver than in adult liver (adducin 3 or <jats:italic><jats:styled-content style=\"fixed-case\">ADD3<\/jats:styled-content><\/jats:italic>). Together, these studies emphasize the importance of the human evidence, and present opportunities to map novel pathways which explain the phenotypic heterogeneity of <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>. <jats:italic>WIREs Syst Biol Med<\/jats:italic> 2015, 7:267\u2013273. doi: 10.1002\/wsbm.1303<\/jats:p><jats:p>This article is categorized under:\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Analytical and Computational Methods &gt; Computational Methods<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Developmental Biology &gt; Developmental Processes in Health and Disease<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Translational, Genomic, and Systems Medicine &gt; Translational Medicine<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wsbm.1303","type":"journal-article","created":{"date-parts":[[2015,5,11]],"date-time":"2015-05-11T11:09:34Z","timestamp":1431342574000},"page":"267-273","source":"Crossref","is-referenced-by-count":21,"title":["Genome\u2010wide association studies in biliary atresia"],"prefix":"10.1002","volume":"7","author":[{"given":"Mylarappa","family":"Ningappa","sequence":"first","affiliation":[{"name":"Department of Surgery, Hillman Center for Pediatric Transplantation Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California San Diego  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon W.","family":"Higgs","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hillman Center for Pediatric Transplantation Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chethan","family":"Ashokkumar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hillman Center for Pediatric Transplantation Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)  Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hillman Center for Pediatric Transplantation Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC)  Pittsburgh PA 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