Large-Scale GWAS Reveals the Association of the Functional Role IL-10 Gene with Susceptibility to Biliary Atresia in the Southern Chinese Population

Biliary atresia (BA) is characterized as an immune-related disorder that involves neonatal biliary obstruction and cholestasis. The aetiology of BA is unclear, and genetic components, environmental factors and immunological responses are involved. In this study, we selected fourteen SNPs in thirteen immune-related genes and investigated their associations with BA by using a large case-control cohort with a total of 503 cases and 1473 controls from southern China. SNP rs1518111 in IL-10 was identified as associated with BA (P=5.79E-03). Epistatic effects of STAT4 and CXCL3, STAT4 and DRAM1, CXCL3 and RAD51B, and IFNG and IL26 were suggested to be associated with BA when we tested the pairwise interactions among these SNPs. Furthermore, we explored the potential role of IL-10 in the pathogenesis of RRV-induced bile duct injury in mice. IL-10 helped to improve the phenotype and inhibit the activation of immune cells in BA mice. In conclusion, this study provided strong evidence implicating IL-10 as a susceptibility gene for BA in a population from southern China. Funding Statement: This study was supported by grant from Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease (No: 2019B030301004). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the institutional review board of the hospital. Informed consent was obtained from the guardians of all patients included in this study.