Dataset Information

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

ABSTRACT:

Background & aims

Collagenous colitis (CC) is an inflammatory bowel disorder with unknown etiopathogenesis involving HLA-related immune-mediated responses and environmental and genetic risk factors. We carried out an array-based genetic association study in a cohort of patients with CC and investigated the common genetic basis between CC and Crohn's disease (CD), ulcerative colitis (UC), and celiac disease.

Methods

DNA from 804 CC formalin-fixed, paraffin-embedded tissue samples was genotyped with Illumina Immunochip. Matching genotype data on control samples and CD, UC, and celiac disease cases were provided by the respective consortia. A discovery association study followed by meta-analysis 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.

Results

Three HLA alleles (HLA-B∗08:01, HLA-DRB1∗03:01, and HLA-DQB1∗02:01), related to the ancestral haplotype 8.1, were significantly associated with increased CC risk. We also identified an independent protective effect of HLA-DRB1∗04:01 on CC risk. Polygenic risk score quantifying the risk across multiple susceptibility loci was strongly associated with CC 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.

Conclusions

In this largest genetic study of CC to date with histologically confirmed diagnosis, we strongly implicated the HLA locus and proposed potential non-HLA mechanisms in disease pathogenesis. We also detected a shared genetic risk between CC, celiac disease, CD, and UC, which supports clinical observations of comorbidity.

SUBMITTER: Stahl E

PROVIDER: S-EPMC7483815 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Stahl Eli E Roda Giulia G Dobbyn Amanda A Hu Jianzhong J Zhang Zhongyang Z Westerlind Helga H Bonfiglio Ferdinando F Raj Towfique T Torres Joana J Chen Anli A Petras Robert R Pardi Darrell S DS Iuga Alina C AC Levi Gabriel S GS Cao Wenqing W Jain Prantesh P Rieder Florian F Gordon Ilyssa O IO Cho Judy H JH D'Amato Mauro M Harpaz Noam N Hao Ke K Colombel Jean Frederic JF Peter Inga I

Gastroenterology 20200501 2

<h4>Background & aims</h4>Collagenous colitis (CC) is an inflammatory bowel disorder with unknown etiopathogenesis involving HLA-related immune-mediated responses and environmental and genetic risk factors. We carried out an array-based genetic association study in a cohort of patients with CC and investigated the common genetic basis between CC and Crohn's disease (CD), ulcerative colitis (UC), and celiac disease.<h4>Methods</h4>DNA from 804 CC formalin-fixed, paraffin-embedded tissue samples w ...[more]

PMID: 32371109

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Dataset Information

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

Background & aims

Methods

Results

Conclusions

Publications

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

Similar Datasets

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