Biliary atresia is associated with polygenic susceptibility in ciliogenesis and planar polarity effector genes.

ABSTRACT:

Background & aims

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.

Methods

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.

Results

A GWAS of common single nucleotide polymorphisms (SNPs), i.e. allele frequencies >1%, identified intronic SNPs rs6446628 in AFAP1 with

SUBMITTER: Glessner JT 

PROVIDER: S-EPMC10729795 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature