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Activity Number: 425 - Novel Methods for Analyzing Genetic and Genomic Data on Complex Diseases
Type: Invited
Date/Time: Thursday, August 6, 2020 : 10:00 AM to 11:50 AM
Sponsor: Section on Statistics in Genomics and Genetics
Abstract #308027
Title: CCmed for Identifying Robust Trans-EQTLs and Assessing Their Effects on Human Traits
Author(s): Fan Yang and Kevin Gleason and Jiebiao Wang and Jubao Duan and Xin He and Brandon Pierce and Lin Chen*
Companies: University of Colorado Anschutz Medical Campus and University of Chicago and University of Pittsburgh and University of Chicago and University of Chicago and University of Chicago and University of Chicago
Keywords: trans-expression quantitative trait loci; mediation analysis; cross-condition; cis-mediated trans-association; two-sample Mendelian Randomization; validation
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 SNPs, we proposed two Cross-Condition Mediation methods -- CCmed(gene) and CCmed(GWAS), 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 CCmed(GWAS), 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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