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

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

Open link

Publication date

February 2021

DOI

10.1038/s41467-021-21458-z

Publisher

Springer Science and Business Media LLC

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...