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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-02-18

AUTHORS

Shixian Hu, Werna T. Uniken Venema, Harm-Jan Westra, Arnau Vich Vila, Ruggero Barbieri, Michiel D. Voskuil, Tjasso Blokzijl, Bernadien H. Jansen, Yanni Li, Mark J. Daly, Ramnik J. Xavier, Gerard Dijkstra, Eleonora A. Festen, Rinse K. Weersma

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. More... »

PAGES

1122

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-021-21458-z

    DOI

    http://dx.doi.org/10.1038/s41467-021-21458-z

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1135434123

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33602935


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