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Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease

Published version
Peer-reviewed

Type

Article

Change log

Authors

Peters, James E 
Lyons, Paul A 
Lee, James C 
Richard, Arianne C 
Fortune, Mary D 

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.

Description

Keywords

1107 Immunology, 0604 Genetics, Biomedical, Basic Science, Autoimmune Disease, Genetics, Human Genome, Digestive Diseases, Generic Health Relevance, Inflammatory and Immune System, 2.1 Biological and endogenous factors

Journal Title

PLOS GENETICS

Conference Name

Journal ISSN

1553-7404

Volume Title

12

Publisher

Rights

CC0 No rights reserved
Sponsorship
This research was funded by a Wellcome Trust Clinical PhD Programme Fellowship (JEP), the NIH-Oxford-Cambridge Scholars Program (ACR), Wellcome Trust Grant 083650/Z/07/Z and MRC Grant MR/L19027/1 (KGCS), and the National Institute for Health Research Cambridge Biomedical Research Centre. KGCS is a National Institute for Health Research Senior Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.