PT  - JOURNAL ARTICLE
AU  - Yang, Fan
AU  - Gleason, Kevin J.
AU  - Wang, Jiebiao
AU  - ,
AU  - Duan, Jubao
AU  - He, Xin
AU  - Pierce, Brandon L
AU  - Chen, Lin S
TI  - CCmed: cross-condition mediation analysis for identifying robust trans-eQTLs and assessing their effects on human traits
AID  - 10.1101/803106
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 803106
4099  - http://biorxiv.org/content/early/2019/10/13/803106.short
4100  - http://biorxiv.org/content/early/2019/10/13/803106.full
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.