biostudies-literatureGlessner JTNIBIB NIH HHSNCATS NIH HHSNIDDK NIH HHSNCRR NIH HHSNHLBI NIH HHS1385-1395https://www.ebi.ac.uk/biostudies/studies/S-EPMC10729795biostudies-literatureUnknown79(6)<h4>Background & aims</h4>Biliary atresia (BA) is poorly understood and leads to liver transplantation (LT), with the requirement for and associated risks of lifelong immunosuppression, in most children. We performed a genome-wide association study (GWAS) to determine the genetic basis of BA.<h4>Methods</h4>We performed a GWAS in 811 European BA cases treated with LT in US, Canadian and UK centers, and 4,654 genetically matched controls. Whole-genome sequencing of 100 cases evaluated synthetic association with rare variants. Functional studies included whole liver transcriptome analysis of 64 BA cases and perturbations in experimental models.<h4>Results</h4>A GWAS of common single nucleotide polymorphisms (SNPs), i.e. allele frequencies >1%, identified intronic SNPs rs6446628 in AFAP1 withJournal of hepatologyBiliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.PMC10729795UL1 TR000130U01 DK062497U01 DK062453U01 DK062470U01 DK103149UL1 TR002378U24 DK062456U01 DK062436UL1 TR002535U01 DK062456R01 HL153407R01 EB028532U01 DK103140U01 DK062481UL1 TR001872U01 DK103135R01 DK109365UL1 TR000423U01 DK084575U01 DK062445U01 DK084538U01 DK062500UM1 TR004399UL1 TR001857U01 DK084536U01 DK062466UL1 TR001878UL1 RR025014R01 EB024562Ningappa MBSo JPaul MHiggs BWSleiman PMASindhi RSchmitt LRajasundaram DGittes GKKelly DVelazquez JWang XSubramaniam SSalgado CMVaccaro CAshokkumar CNarayanan TLi DHorslen SZahid MSharif KMarch MEbrahimkhani MRBillings JPrasadan KSquires RDhawan ALo CWReyes-Mugica MShin DHakonarson HPellegrino RNgo KAGlessner JTRanganathan SfalseBiliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.<h4>Background & aims</h4>Biliary atresia (BA) is poorly understood and leads to liver transplantation (LT), with the requirement for and associated risks of lifelong immunosuppression, in most children. We performed a genome-wide association study (GWAS) to determine the genetic basis of BA.<h4>Methods</h4>We performed a GWAS in 811 European BA cases treated with LT in US, Canadian and UK centers, and 4,654 genetically matched controls. Whole-genome sequencing of 100 cases evaluated synthetic association with rare variants. Functional studies included whole liver transcriptome analysis of 64 BA cases and perturbations in experimental models.<h4>Results</h4>A GWAS of common single nucleotide polymorphisms (SNPs), i.e. allele frequencies >1%, identified intronic SNPs rs6446628 in AFAP1 with2023-01-01T00:00:00Z2023 Dec2026-05-28T08:45:28.55Z2024-11-13T17:22:50.876ZS-EPMC107297953757279410.1016/j.jhep.2023.07.039