Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease

Abstract

Background: Recent studies discovered many genetic variants associated with both psychiatric and inflammatory disorders, but the role of genetic factors in the development of psychiatric comorbidity (PC) in inflammatory bowel disease (IBD) is underexplored. Particularly, it has been shown that some of the genetic variants have been linked to the concentrations of circulating cytokines and symptoms of the inflammatory cytokine-associated depression. We analysed genomic features of individuals with IBD by comparing IBD patients with PC with those who have IBD but without PC. We hypothesized that cytokine related signaling pathways may be significantly associated with the psychiatric comorbidity in patients with IBD.Methods: Individuals enrolled in the Manitoba IBD Cohort Study were separated to two groups accordingly to the presence of PC. A sample set comprising 97 IBD individuals with PC (IBD+PC) and 146 IBD individuals without PC (IBD) was first used to identify copy number variations (CNVs) from genome-wide genetic data using three different detection algorithms. IBD+PC and IBD groups were compared by the number of CNVs overlapping each gene; deletions and duplications were analysed separately. Gene set overrepresentation analysis was then conducted using CNV-overlapped genes and the candidate gene sets of neurological and immunological relevance.Results: Medium-sized CNV (size between 100 and 500 kilobase pairs)-burden is significantly higher in IBD+PC than IBD groups. Gene-based CNV association analysis did not show significant differences between the two IBD groups. Gene set overrepresentation analysis

Polygenic risk and causal inference of psychiatric comorbidity in inflammatory bowel disease among patients with European ancestry

“…Samples for this study were collected from the Manitoba IBD Cohort Study which was initiated in 2002 [ 22 ]. The genetic profiles of the same samples were used for the previous CNV and transcriptome-wide analysis [ 20 , 21 ]. The Manitoba IBD Cohort Study enrolled participants from the University of Manitoba IBD Research Registry.…”

“…This produced the genotype data for 2,372,784 SNPs for each individual. The quantity control (QC) was performed by PLINK version 1.9 [ 26 ] as described in the previous papers [ 20 , 21 ]. In short, SNPs with missing rate 0.05, minor allele frequency < 0.05, and p-value < 5 × 10 –5 for Hardy–Weinberg equilibrium were removed.…”

“…Although there are many GWAS of IBD [ 16 , 17 ], there are limited GWAS analyses of PC in IBD. Recently, we performed one of the first genome-wide copy number variation (CNV) analysis [ 20 ] and transcriptome-wide analysis of PC in IBD [ 21 ], which suggested that the expression level of the RBPMS gene has an association with PC status in persons with IBD [ 20 , 21 ]. Gene expression has been considered as a mediator between genetic variants and disease phenotype [ 22 ].…”

Genome-wide copy number variant data for inflammatory bowel disease in a caucasian population

“…The presented report is a description of the CNVs identified in 243 IBD patients with Caucasian ethnicity enrolled in the Manitoba IBD Cohort Study [1]. We genotyped 269 individuals with IBD using the Illumina Omni2.5M − 8 microarray.…”

Coriolus Versicolor Downregulates TLR4/NF-κB Signaling Cascade in Dinitrobenzenesulfonic Acid-Treated Mice: A Possible Mechanism for the Anti-Colitis Effect

“…What has certainly been observed over the years is that both types of IBD are characterized by an increase in pro-inflammatory cytokines, chemokines, and adhesion molecules that increase the damage to the barrier function and perpetuate the inflammatory process [ 4 , 5 ]. To confirm this there are studies conducted on mucous biopsies of patients with IBD [ 6 ].…”