CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits

Yang, F.; Gleason, K. J.; Wang, J.; The GTEx Consortium,; Duan, J.; He, X.; Pierce, B. L.; Chen, L. S.

doi:10.1101/803106

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bioRxiv · 10.1101/803106

CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits

Yang, F.·Gleason, K. J.·Wang, J.·The GTEx Consortium,·Duan, J.·He, X.·Pierce, B. L.·Chen, L. S.

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Abstract

Trans-eQTLs collectively explain a substantial proportion of expression variation, yet are challenging to detect and replicate since their effects are individually weak. Many trans-effects are mediated by cis-gene expression and some of those effects are shared across tissue types/conditions. To detect robust cis-mediated trans-associations at the gene-level and for specific single nucleotide polymorphisms (SNPs), we proposed two Cross-Condition Mediation methods - CCmedgene and CCmedGWAS, respectively. We analyzed data from 13 brain tissue types from the Genotype-Tissue Expression (GTEx) project, and identified trios with cis-eQTLs of a cis-gene having associations with a trans-gene, many of which show evidence of replication in other datasets. By applying CCmedGWAS, we identified trans-genes associated with known schizophrenia susceptibility loci. We further conducted validation analyses assessing the schizophrenia-risk-associations of the identified trans-genes, by harnessing GWAS summary statistics from the Psychiatric Genomics Consortium and multitissue eQTL statistics from GTEx.

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Yang, F., Gleason, K. J., Wang, J., The GTEx Consortium,, Duan, J., He, X., Pierce, B. L., Chen, L. S.. 2019-10-13. CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits. https://doi.org/10.1101/803106

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