RT Journal Article
SR Electronic
T1 Stratified Linkage Disequilibrium Score Regression reveals enrichment of eQTL effects on complex traits is not tissue specific
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 107482
DO 10.1101/107482
A1 Hill F. Ip
A1 Rick Jansen
A1 Abdel Abdellaoui
A1 Meike Bartels
A1 UK Brain Expression Consortium
A1 Dorret I. Boomsma
A1 Michel G. Nivard
YR 2017
UL http://biorxiv.org/content/early/2017/06/22/107482.abstract
AB Both gene expression levels and eQTLs (expression quantitative trait loci) are partially tissue-specific, complicating the detection of eQTLs in tissues with limited sample availability, such as the brain. However, eQTL overlap between tissues might be non-trivial, allowing for inference of eQTL functioning in the brain via eQTLs measured in readily accessible tissues, e.g. whole blood. Using Stratified Linkage Disequilibrium Score Regression (SLDSR), we quantify the enrichment in GWAS signal of blood and brain eQTLs in genome-wide association study (GWAS) for three brain-related (schizophrenia, BMI, and educational attainment), three immune-related traits (Crohn’s disease, rheumatoid arthritis, and ulcerative colitis), and five traits not strongly associated with either tissue (age at menarche, coronary artery disease, height, LDL levels, and smoking behavior). Our analyses established significant enrichment of blood and brain eQTLs in their effects across all traits. As we do not know the true number of causal eQTLs, it is difficult to determine the precise magnitude of enrichment. We found no evidence for tissue-specific enrichment in GWAS signal for either eQTLs uniquely seen in the brain or whole blood. To follow up on our findings, we tested tissue-specific enrichment of eQTLs discovered in 44 tissues by the Genotype-Tissue Expression (GTEx) consortium, and, again, found no tissue-specific eQTL effects. Finally, we integrated the GTEx eQTLs with SNPs associated with tissue-specific histone modifiers, and interrogated its effect on rheumatoid arthritis and schizophrenia. We observed substantially enriched effects on schizophrenia, though again not tissue-specific. We conclude that, while eQTLs are strongly enriched in GWAS signal, the enrichment is not specific to the tissue used in eQTL discovery. Therefore, working with relatively accessible tissues, such as whole blood, as proxy for eQTL discovery is sensible and restricting lookups for GWAS hits to a specific tissue might not be advisable.