Trans-eQTLs Can Be Used to Identify Tissue-Specific Gene Regulatory Networks

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to find tissue-specific gene regulatory networks. eQTL data for 19,960 genes were obtained from the eQTLGen study. Next, eQTLs that display both cis and trans regulatory effects (P<5e-8) were selected and the association between their corresponding genes were examined by Mendelian randomization. The findings were once more validated using eQTL data from the INTERVAL study. The trans-regulatory impact of 138 genes on 342 genes were detected (P≤5e-8). Majority of the identified gene-pairs aggregated into networks with scale free topology. Examining the function of genes indicated they are involved in immune processes. The hub genes mainly shared transcription regulation activity. On average a gene in the network was under the regulatory control of 34 cis-eQTLs and 6 trans-eQTLs and genes with higher heritability tended to exert higher regulatory impact. This study indicates tissue-specific gene-regulatory networks can be detected by investigating their genomic underpinnings. The identified networks displayed scale-free topology indicating hub genes of a network could be targeted to correct abnormalities at cellular level.