Genetic association and causal effects between inflammatory bowel disease and conjunctivitis.

Abstract

Inflammatory bowel disease (IBD) is often clinically associated with conjunctivitis, which may result from genetic associations and causal effects. Genetic correlations were investigated through the genome-wide association study (GWAS) data on IBD and conjunctivitis using the linkage disequilibrium score regression (LDSC) and heritability estimated in summary statistics (HESS). The causal effect analysis was performed using four methods of Mendelian randomization (MR) and the genetic risk loci common to both diseases were identified by the statistical method of conditional/conjoint false discovery rate (cond/conjFDR), followed by genetic overlap analysis. Finally, a multi-trait GWAS analysis (MTAG) was performed to validate the identified shared loci. IBD (including CD and UC) and conjunctivitis showed a significant overall correlation at the genomic level; however, the local correlation of IBD and CD with conjunctivitis was significant and limited to chromosome 11. MR analysis suggested a significant positive and non-significant negative correlation between IBD (including CD and UC) and conjunctivitis. The conjFDR analysis confirmed the genetic overlap between the two diseases. Additionally, MTAG was employed to identify and validate multiple genetic risk loci. The present study provides evidence of genetic structure and causal effects for the co-morbidity between IBD (both CD and UC) and conjunctivitis, expanding the epidemiologic understanding of the two diseases.