Collagenous Colitis Shares Genetic Risk with Other Immune-Mediated Diseases

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An array-based, genetic association study was carried out in a cohort of patients with collagenous colitis (CC) and the common genetic basis was investigated between that and Crohn’s disease (CD), ulcerative colitis (UC), and celiac disease.

DNA from 804 CC formalin-fixed, paraffinembedded tissue samples were genotyped with Illumina Immunochip. Matching genotype data was carried out on control samples and CD, UC, and celiac cases were provided by the respective consortia.

A discovery association study followed by metaanalysis with an independent cohort, polygenic risk score calculation and cross-phenotype analyses were performed. Enrichment of regulatory expression, quantitative trait loci among the CC variants was assessed in hemopoietic and intestinal cells.

Three HLA alleles (HLA-B08:01, HLADRB103:01 and HLA-DQB1*02:01), related to the ancestral haplotype 8.1, were significantly associated with increased CC risk. An independent protective effect on HLADRB04; 01 was noted on CC risk. Polygenic risk score quantifying the risk across multiple susceptibility loci was strongly associated with CCI risk.

An enrichment of expression quantitative trait loci was detected among the CC susceptibility variants in various cell types. The cross-phenotype analysis identified a complex pattern of polygenic pleiotropy between CC and other immune-mediated diseases.

It was concluded in this largest genetic study of CC to date, with histologically confirmed diagnosis, this strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. A shared genetic risk was also detected between CC, celiac disease, CD and UC, supporting clinical observations of comorbidity.

Stahl, E., Roda, G., Dobbyn, A., et al. “Collagenous Colitis is Associated with HLA Signature and Shares Genetic Risks with Other Immune-Mediated Diseases.” Gastroenterology 2020; Vol. 159, pp. 549-561.

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