Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia

Hum Genet. 2014 Feb;133(2):235-43. doi: 10.1007/s00439-013-1368-2. Epub 2013 Oct 9.


In the United States, biliary atresia (BA) is the most frequent indication for liver transplantation in pediatric patients. BA is a complex disease, with suspected environmental and genetic risk factors. A genome-wide association study in Chinese patients identified association to the 10q24.2 (hg18) genomic region. This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in intrahepatic bile ducts. We tested association to this region in 171 BA patients and 1,630 controls of European descent and found the strongest signal to be at rs7099604 (p = 2.5 × 10(-3)) in intron 1 of the ADD3 gene. Moreover, expression data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA patients. The role of ADD3 in biliary development is unclear, but our findings suggest that this gene may be functionally relevant for the development of BA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Biliary Atresia / genetics*
  • Biliary Atresia / metabolism
  • Biopsy
  • Calmodulin-Binding Proteins / genetics*
  • Calmodulin-Binding Proteins / metabolism
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics*
  • Cohort Studies
  • European Continental Ancestry Group / genetics
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Genotype
  • Humans
  • Infant
  • Linkage Disequilibrium
  • Liver / metabolism
  • Liver / pathology
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Sequence Analysis, DNA
  • United States


  • ADD3 protein, human
  • Calmodulin-Binding Proteins
  • Aminopeptidases
  • X-Pro aminopeptidase