A novel susceptibility locus in MST1 and gene-gene interaction network for Crohn's disease in the Chinese population

The incidence of Crohn's disease is increasing in many Asian countries, but considerable differences in genetic susceptibility have been reported between Western and Asian populations. This study aimed to fine-map 23 previously reported Crohn's disease genes and identify their interactions in the Chinese population by Illumina-based targeted capture sequencing. Our results showed that the genetic polymorphism A>G at rs144982232 in MST1 showed the most significant association (P = 1.78 × 10^-5 ; odds ratio = 4.87). JAK2 rs1159782 (T>C) was also strongly associated with Crohn's disease (P = 2.34 × 10^-4 ; odds ratio = 3.72). Gene-gene interaction analysis revealed significant interactions between MST1 and other susceptibility genes, including NOD2, MUC19 and ATG16L1 in contributing to Crohn's disease risk. Main genetic associations and gene-gene interactions were verified using ImmunoChip data set. In conclusion, a novel susceptibility locus in MST1 was identified. Our analysis suggests that MST1 might interact with key susceptibility genes involved in autophagy and bacterial recognition. These findings provide insight into the genetic architecture of Crohn's disease in Chinese and may partially explain the disparity of genetic signals in Crohn's disease susceptibility across different ethnic populations by highlighting the contribution of gene-gene interactions.