Systematic identification of trans eQTLs as putative drivers of known disease associations
Harm-Jan Westra1, Marjolein J Peters2,3, Tõnu Esko4
1Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen, the Netherlands.
Abstract:
Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3' UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
More Related Videos
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Pharmacogenomics: Identification of New Drug Targets
Genetic Screens
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...


