[PMID:28218759] [Nature Genetics]
“GWAS loci are also enriched in expression quantitative trait loci (eQTLs), thus suggesting that most risk variants alter gene expression. However, because causal variants are difficult to identify, and cis-eQTLs occur frequently, it remains challenging to identify specific instances of disease-relevant changes to gene regulation…Using eQTLs from three major immune subpopulations, we found shared effects in only ~25% of the loci examined. Thus, we show that a fraction of gene-regulatory changes suggest strong mechanistic hypotheses for disease risk, but we conclude that most risk mechanisms are not likely to involve changes in basal gene expression.”
[PMID:28362817] [PLoS Genetics]
“to examine associations between imputed gene expression and breast cancer risk. In particular, we used reference datasets describing the breast tissue and whole blood transcriptomes to impute expression levels in breast cancer cases and controls.” Five eQTL genes are suggested to be associated with breast cancer risk, two of them are GWAS hits. “Among the genetic variants that contributed to the predicted expression of the five genes, we found 23 nominally (p-value < 0.05) associated with breast cancer risk, among which 15 are not in high linkage disequilibrium with risk variants previously identified by GWAS.”
Long to short, the overlapping/shared effects of eQTLs and GWAS hits might not as high as previously expected.
In addition, recent studies looked at trans-eQTL and found out potential mechanisms.
[PMID:28285768] [American Journal of Human Genetics]
eQTL analysis on whole blood gene expression measurements from 5,257 participants in the Framingham Heart Study (FHS) and 39,165 trait-associated SNPs identified from GWASs. “We hypothesized that some trans-eQTLs regulate expression of distant genes by altering the expression of nearby genes (cis-eGenes).” “we identified 13 trans-eQTL hotspots (trans-eQTLs that simultaneously affect the expression of many distant target genes), affecting from ten to hundreds of genes, suggesting the existence of master genetic regulators.” The effect of the causal trans-eQTL is likely to be mediated by a cis-eGene. Importantly, these causal loci were not detected by traditional GWAS approaches.
[PMID:28285767] [American Journal of Human Genetics]
The authors applied cross-phenotype meta-analysis (CPMA) statistic to expression data from lymphoblastoid cell lines (9,085 genes, 322 individuals) and 737,867 autosomal markers across three African HapMap populations, and identified 16,484 candidate trans-eQTL hotspots. In contrast to the study mentioned above [PMID:28285768], no cis-eQTL effects were detected for any of the eight hotspots.