RT Journal Article
SR Electronic
T1 CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 803106
DO 10.1101/803106
A1 Yang, Fan
A1 Gleason, Kevin J.
A1 Wang, Jiebiao
A1 ,
A1 Duan, Jubao
A1 He, Xin
A1 Pierce, Brandon L
A1 Chen, Lin S
YR 2019
UL http://biorxiv.org/content/early/2019/10/13/803106.abstract
AB 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.