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

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 and Rinse K. Weersma ()
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Shixian Hu: University of Groningen and University Medical Center Groningen
Werna T. Uniken Venema: University of Groningen and University Medical Center Groningen
Harm-Jan Westra: University of Groningen and University Medical Center Groningen
Arnau Vich Vila: University of Groningen and University Medical Center Groningen
Ruggero Barbieri: University of Groningen and University Medical Center Groningen
Michiel D. Voskuil: University of Groningen and University Medical Center Groningen
Tjasso Blokzijl: University of Groningen and University Medical Center Groningen
Bernadien H. Jansen: University of Groningen and University Medical Center Groningen
Yanni Li: University of Groningen and University Medical Center Groningen
Mark J. Daly: Broad Institute of Harvard and Massachusetts Institute of Technology
Ramnik J. Xavier: Broad Institute of Harvard and Massachusetts Institute of Technology
Gerard Dijkstra: University of Groningen and University Medical Center Groningen
Eleonora A. Festen: University of Groningen and University Medical Center Groningen
Rinse K. Weersma: University of Groningen and University Medical Center Groningen

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: 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

Date: 2021
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DOI: 10.1038/s41467-021-21458-z

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