UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Characterizing the Relation Between Expression QTLs and Complex Traits: Exploring the Role of Tissue Specificity

Ip, HF; Jansen, R; Abdellaoui, A; Bartels, M; UK Brain Expression Consortium, .; Boomsma, DI; Nivard, MG; (2018) Characterizing the Relation Between Expression QTLs and Complex Traits: Exploring the Role of Tissue Specificity. Behavior Genetics , 48 (5) pp. 374-385. 10.1007/s10519-018-9914-2. Green open access

[thumbnail of 10.1007_s10519-018-9914-2.pdf]
Preview
Text
10.1007_s10519-018-9914-2.pdf - Published Version

Download (1MB) | Preview

Abstract

Measurement of gene expression levels and detection of eQTLs (expression quantitative trait loci) are difficult in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be high, which would allow for inference of eQTL functioning in the brain via eQTLs detected in readily accessible tissues, e.g. whole blood. Applying Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantified the enrichment in polygenic signal of blood and brain eQTLs in genome-wide association studies (GWAS) of 11 complex traits. We looked at eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium and two other large representative studies, and found no tissue-specific eQTL effects. Next, we integrated the GTEx eQTLs with regions associated with tissue-specific histone modifiers, and interrogated their effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects of eQTLs located inside regions bearing modification H3K4me1 on schizophrenia, but not rheumatoid arthritis, and not tissue-specific. Finally, we extracted eQTLs associated with tissue-specific differentially expressed genes and determined their effects on rheumatoid arthritis and schizophrenia, these analysis revealed limited enrichment of eQTLs associated with gene specifically expressed in specific tissues. Our results pointed to strong enrichment of eQTLs in their effect on complex traits, without evidence for tissue-specific effects. Lack of tissue-specificity can be either due to a lack of statistical power or due to the true absence of tissue-specific effects. We conclude that eQTLs are strongly enriched in GWAS signal and that the enrichment is not specific to the eQTL discovery tissue. Until sample sizes for eQTL discovery grow sufficiently large, working with relatively accessible tissues as proxy for eQTL discovery is sensible and restricting lookups for GWAS hits to a specific tissue for which limited samples are available might not be advisable.

Type: Article
Title: Characterizing the Relation Between Expression QTLs and Complex Traits: Exploring the Role of Tissue Specificity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s10519-018-9914-2
Publisher version: https://doi.org/10.1007/s10519-018-9914-2
Language: English
Additional information: © The Author(s) 2018. Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Keywords: Brain, Complex human traits, Enrichment, Gene expression, Genome-wide, SLDSR, Stratified linkage disequilibrium score regression, Tissue-specificity, Whole blood, eQTL discovery
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10055150
Downloads since deposit
83Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item