Multiple susceptibility enhancer variants increasing <i>ADD3</i> expression predisposes to biliary atresia risk.

ABSTRACT:

Background

Non-syndromic biliary atresia (BA) is a multifactorial disorder with a poorly understood genetic basis. We previously identified 154 BA-associated SNPs spanning the ADD3 locus, which harbors the most strongly associated common variants in Asian populations. The susceptibility SNPs are in high linkage disequilibrium, but the causal variants remain unidentified.

Methods

Using available databases, we predicted the regulatory potential of the 154 BA-associated SNPs. To functionally validate these findings, we assessed the enhancer activity of cis-regulatory elements (CREs) containing the risk variants using a dual-luciferase reporter assay. The role of ADD3 dysregulation in hepatobiliary development was investigated using zebrafish. The spatiotemp

SUBMITTER: Han X 

PROVIDER: S-EPMC12832116 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature