Genetic Colocalization in Inflammatory Bowel Disease Tissues to Detect Potentially Causal Variants

Crohn’s disease and other inflammatory bowel diseases (IBD) are diseases of the gastrointestinal tract with great heterogeneity in presentation and severity. Genome wide association studies (GWAS) have already identified over 200 loci associated with IBD. While the current data provides a vast amount of information on genetic associations, little is known about the causal mechanisms with which these genes act. Significant expression quantitative trait loci (eQTL) have also been identified in tissues impacted by IBD. These eQTL provide information linking genetic variants to mRNA expression in target genes. This study investigates inflammatory bowel diseases by colocalizing significant eQTL loci with IBD GWAS loci to determine the probability of a shared causal variant. We hypothesize that where a causal variant is shared, the change in gene expression detected by eQTLs may be mediating the phenotypic response associated with a GWAS loci. To detect the presence of causal variants, eQTL were colocalized with 241 known GWAS loci using linkage disequilibrium and a bayesian colocalization method, Coloc. We found high probability for the existence of casual variants for several significant eQTL colocalized with GWAS loci in the same genetic region, including SNPs associated with the gene FUT2. These findings demonstrate the existence of causal genetic variants contributing to the variation found in inflammatory bowel diseases and can be used to further study the genetic contributions to disease.