LAUSR

BACKGROUND Inflammatory bowel disease (IBD) affects millions of people in North America, and patients with IBD have a high incidence of psychiatric comorbidities (PC). The genetic mechanisms underlying the link are, in general, poorly understood. MATERIALS AND METHODS A transcriptome-wide association study (TWAS) was performed using genetically regulated gene expression profiles imputed from the genetic profiles of 240 IBD patients in the Manitoba IBD Cohort Study. The imputation was performed using the 44 non-diseased human tissue-specific reference models from the GTEx database. Linear modeling and gene set enrichment analysis were performed to identify genes and pathways that are significantly associated with IBD patients with PC compared to IBD alone in each of the 44 non-diseased human tissues. Finally, an enrichment map was generated to investigate networks of the enriched gene sets associated with IBD patients with PC. RESULTS The genes RBPMS in skeletal muscle (adjusted p = 0.05), KCNA5 in the cerebellar hemisphere of the brain (adjusted p = 0.09), GSR, SMIM34A, and LIPT2 in the frontal cortex of the brain (adjusted p = 0.09 for each) were the top genetically regulated genes with a suggestive association with IBD patients with PC. We identified three gene set networks, which include gene sets and pathways with a suggestive association with IBD patients with PC: one with 7 gene sets overlapping in apolipoprotein B mRNA editing subunit genes, one with 3 gene sets including pigmentation gene sets, and the other one with 3 gene sets including peptidyl tyrosine phosphorylation regulation related gene sets. CONCLUSIONS Our TWAS analysis has identified genes and pathways with a suggestive association with IBD patients with PC. These findings can be potentially used for illustrating the mechanism of developing PC in the patients with IBD and developing diagnosis tool or drug targets for IBD patients with PC.