Collagenous Colitis Is Associated With HLA Signature and Shares Genetic Risks With Other Immune-Mediated Diseases

Area of Science:

• Genetics
• Immunology
• Gastroenterology

Background:

• Collagenous colitis (CC) is an inflammatory bowel disorder with an unclear cause.
• CC pathogenesis may involve immune responses linked to HLA, genetics, and environmental factors.

Purpose of the Study:

• To conduct a genetic association study in CC patients.
• To investigate shared genetic underpinnings between CC and other immune-mediated diseases like Crohn's disease (CD), ulcerative colitis (UC), and celiac disease.

Main Methods:

• Genotyping of 804 CC tissue samples using Illumina Immunochip.
• Meta-analysis with independent cohorts and polygenic risk score calculation.
• Cross-phenotype analyses and assessment of expression quantitative trait loci (eQTLs) in various cell types.

Main Results:

• Significant association of three HLA alleles (HLA-B∗08:01, HLA-DRB1∗03:01, HLA-DQB1∗02:01) with increased CC risk.
• Identification of a protective effect for HLA-DRB1∗04:01.
• Strong association of polygenic risk scores with CC risk and enrichment of eQTLs in CC-susceptibility variants.

Conclusions:

• The HLA locus is strongly implicated in CC pathogenesis.
• Potential non-HLA mechanisms contribute to CC development.
• Shared genetic risk between CC, celiac disease, CD, and UC supports clinical comorbidity observations.