Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility

Abstract

Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of <i>ADD3</i>, <i>GPC1</i>, <i>ARF6</i>, and <i>EFEMP1</i> 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 <i>ADD3</i> were significantly associated with BA, and rs17095355 was the top SNP (<i>P</i>_Allele = 3.23×10^-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 <i>ADD3</i>. Two <i>GPC1</i> SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility (<i>P</i>_Allele = 0.03 for rs6707262 and <i>P</i>_Allele = 0.04 for rs6750380), and were eQTL of <i>GPC1</i>. Haplotype harboring these two SNPs almost reached the study-wide significance (<i>P</i> = 0.0035). No association for <i>ARF6</i> and <i>EFEMP1</i> was found with BA risk in the current population. Our study validated associations of <i>ADD3</i> and <i>GPC1</i> SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.