Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility
Open Access
- 30 April 2020
- journal article
- research article
- Published by Impact Journals, LLC in Aging
- Vol. 12 (8), 7163-7182
- https://doi.org/10.18632/aging.103067
Abstract
Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of ADD3, GPC1, ARF6, and EFEMP1 gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population. Twenty single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 340 BA patients and 1,665 controls. Three SNPs in ADD3 were significantly associated with BA, and rs17095355 was the top SNP (P-Allele = 3.23x10(-6)). Meta-analysis of published data and current data indicated that rs17095355 was associated with BA susceptibility in Asians and Caucasians. Three associated SNPs were expression quantitative trait loci (eQTL) for ADD3. Two GPC1 SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility (P-Allele = 0.03 for rs6707262 and P-Allele = 0.04 for rs6750380), and were eQTL of GPC1. Haplotype harboring these two SNPs almost reached the study-wide significance (P = 0.0035). No association for ARF6 and EFEMP1 was found with BA risk in the current population. Our study validated associations of ADD3 and GPC1 SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.This publication has 40 references indexed in Scilit:
- A linear complexity phasing method for thousands of genomesNature Methods, 2011
- pROC: an open-source package for R and S+ to analyze and compare ROC curvesBMC Bioinformatics, 2011
- Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresiaHepatology, 2011
- Adducins Regulate Remodeling of Apical Junctions in Human Epithelial CellsMolecular Biology of the Cell, 2010
- Genome-wide association study identifies a susceptibility locus for biliary atresia on 10q24.2Human Molecular Genetics, 2010
- Genomic alterations in biliary atresia suggest region of potential disease susceptibility in 2q37.3American Journal of Medical Genetics Part A, 2010
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- A Generalized Combinatorial Approach for Detecting Gene-by-Gene and Gene-by-Environment Interactions with Application to Nicotine DependenceAmerican Journal of Human Genetics, 2007
- Haploview: analysis and visualization of LD and haplotype mapsBioinformatics, 2004
- The significance of human jagged 1 mutations detected in severe cases of extrahepatic biliary atresiaHepatology, 2002