Genetic overlap between inflammatory bowel disease and iridocyclitis: insights from a genome-wide association study in a European population

BACKGROUND: Inflammatory bowel disease (IBD) is occasionally associated with ophthalmic diseases, including iridocyclitis (IC). The co-occurrence of IBD and IC has been increasingly observed, possibly due to shared genetic structures. METHODS: A three-part analysis was executed utilizing genome-wide association study (GWAS) data on IBD and IC. First, the overall genetic correlation between the two traits was observed using linkage disequilibrium score regression (LDSC). Subsequent to this, a local genetic correlation analysis was conducted utilizing the heritability estimation from summary statistics (HESS) methodology. Finally, the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework was utilized to ascertain the degree of genetic overlap between the two traits. RESULTS: Positive overall correlations were observed among IBD, ulcerative colitis (UC), and IC, encompassing both acute/subacute and chronic IC presentations. While a significant correlation was identified between Crohn's disease (CD) and IC, it was not evident for acute/subacute or chronic IC (P > 0.05). Notably, IBD (encompassing CD and UC) demonstrated local genetic correlations with IC and acute/subacute IC, with pronounced enrichment notably on chromosomes 1 and 6, though such correlations were not observed with chronic IC. The conjFDR analysis confirmed the genetic overlap between the two diseases. The shared genes overlapping between IBD (encompassing CD and UC) and IC were IL23R, GPR35, and ERAP1. For acute/subacute IC and chronic IC, there were six overlapping genes (GPR35, RPL23AP12, IL23R, SNAPC4, ERAP1, and INAVA) and one overlapping gene (INAVA), respectively. CONCLUSION: This study confirms the existence of a shared genetic structure between IBD and IC, providing a biological basis for their comorbidity. Additionally, this finding has significant implications for preventing and treating these two diseases.