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Cited by 59Inflammatory Bowel DiseaseGenetic Associations and EpidemiologyMultiple Sclerosis Research Studies

Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease

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Hu, Shixian, Uniken Venema, Werna T., Westra, Harm-Jan, Vich Vila, Arnau, Barbieri, Ruggero, Voskuil, Michiel D., Blokzijl, Tjasso, Jansen, Bernadien H. +6 more·2021·Nature Communications
DOI 10.1038/s41467-021-21458-zPMC PMC7892863
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Abstract

More than 240 genetic risk loci have been associated with inflammatory bowel disease (IBD), but little is known about how they contribute to disease development in involved tissue. Here, we hypothesized that host genetic variation affects gene expression in an inflammation-dependent way, and investigated 299 snap-frozen intestinal biopsies from inflamed and non-inflamed mucosa from 171 IBD patients. RNA-sequencing was performed, and genotypes were determined using whole exome sequencing and genome wide genotyping. In total, 28,746 genes and 6,894,979 SNPs were included. Linear mixed models identified 8,881 independent intestinal cis-expression quantitative trait loci (cis-eQTLs) (FDR < 0.05) and interaction analysis revealed 190 inflammation-dependent intestinal cis-eQTLs (FDR < 0.05), including known IBD-risk genes and genes encoding immune-cell receptors and antibodies. The inflammation-dependent cis-eQTL SNPs (eSNPs) mainly interact with prevalence of immune cell types. Inflammation-dependent intestinal cis-eQTLs reveal genetic susceptibility under inflammatory conditions that can help identify the cell types involved in and the pathways underlying inflammation, knowledge that may guide future drug development and profile patients for precision medicine in IBD.

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  • DEGs between inflamed and non-inflamed biopsies significantly overlap with the top-ranked TGs of STAT1 (one-sided bootstrap hypothesis testing).

    “Apart from GWAS-relevant genes, we collected the DEGs between inflamed biopsies and non-inflamed biopsies71 and we found that these DEGs significantly overlapped with the top-ranked TGs of STAT1 (one-sided bootstrap hypothesis testing; Fig. 5e).”

    From Inferring gene regulatory networks from single-cell multiome data using atlas-scale external data (2025) · cites this paper as [71]

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Authors
Hu, S., Uniken Venema, W. T., Westra, H.-J., Vich Vila, A., Barbieri, R., Voskuil, M. D., Blokzijl, T., Jansen, B. H., Li, Y., Daly, M. J., Xavier, R. J., Dijkstra, G., Festen, E. A., & Weersma, R. K.
Affiliations
  • University Medical Center Groningen (NL)
  • Broad Institute (US)
Corresponding author
Weersma, Rinse K.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-02-18
Volume
12
Issue
1
Pages
1122-1122
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-21458-z
PMC
PMC7892863
OpenAlex
W3131620884
Cited by
59
References
4
Citations by year
2026: 10 · 2025: 16 · 2024: 9 · 2023: 16 · 2022: 5 · 2021: 3
FWCI
5.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (RC2DK114784, P30DK043351)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
inflammatory bowel disease, intestinal gene expression, cis-eQTL, genetic susceptibility, immune cell types, host genetic variation, precision medicine
MeSH terms
Adult, Female, Gene Expression Regulation, Humans, Inflammation, Intestines, Male, Genetic Variation, Inflammatory Bowel Diseases, Cohort Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci

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