Insight into genotype-phenotype associations through eQTL mapping in multiple cell types in health and immune-mediated disease
Author(s)
Type
Journal Article
Abstract
Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91), anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46) and healthy controls (n = 43), revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.
Date Issued
2016-03-25
Date Acceptance
2016-02-09
Citation
PLoS Genetics, 2016, 12 (3), pp.1-29
ISSN
1553-7390
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
29
Journal / Book Title
PLoS Genetics
Volume
12
Issue
3
Copyright Statement
© 2016 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000373268900020&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
GENOME-WIDE ASSOCIATION
INFLAMMATORY-BOWEL-DISEASE
GENE-EXPRESSION
RHEUMATOID-ARTHRITIS
SUSCEPTIBILITY LOCI
PREDICTS PROGNOSIS
INCREASED POWER
T-CELLS
VARIANTS
AUTOIMMUNE
Publication Status
Published
Article Number
ARTN e1005908