1. Replication of a GWAS signal in a Caucasian population implicates ADD3 in susceptibility to biliary atresia.
- Author
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Tsai EA, Grochowski CM, Loomes KM, Bessho K, Hakonarson H, Bezerra JA, Russo PA, Haber BA, Spinner NB, and Devoto M
- Subjects
- Aminopeptidases genetics, Aminopeptidases metabolism, Biliary Atresia metabolism, Biopsy, Calmodulin-Binding Proteins metabolism, Chromosome Mapping, Cohort Studies, Gene Expression Regulation, Genetic Predisposition to Disease, Genotype, Humans, Infant, Linkage Disequilibrium, Liver metabolism, Liver pathology, Oligonucleotide Array Sequence Analysis, Sequence Analysis, DNA, United States, White People genetics, Biliary Atresia genetics, Calmodulin-Binding Proteins genetics, Chromosomes, Human, Pair 10 genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
- Abstract
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.
- Published
- 2014
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