TY - JOUR T1 - Co-localization of Conditional eQTL and GWAS Signatures in Schizophrenia JF - bioRxiv DO - 10.1101/129429 SP - 129429 AU - Amanda Dobbyn AU - Laura M. Huckins AU - James Boocock AU - Laura G. Sloofman AU - Benjamin S. Glicksberg AU - Claudia Giambartolomei AU - Gabriel Hoffman AU - Thanneer Perumal AU - Kiran Girdhar AU - Yan Jiang AU - Douglas M. Ruderfer AU - Robin S. Kramer AU - Dalila Pinto AU - the CommonMind Consortium AU - Schahram Akbarian AU - Panos Roussos AU - Enrico Domenici AU - Bernie Devlin AU - Pamela Sklar AU - Eli A. Stahl AU - Solveig K. Sieberts Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/25/129429.abstract N2 - Causal genes and variants within genome-wide association study (GWAS) loci can be identified by integrating GWAS statistics with expression quantitative trait loci (eQTL) and determining which SNPs underlie both GWAS and eQTL signals. Most analyses, however, consider only the marginal eQTL signal, rather than dissecting this signal into multiple independent eQTL for each gene. Here we show that analyzing conditional eQTL signatures, which could be important under specific cellular or temporal contexts, leads to improved fine mapping of GWAS associations. Using genotypes and gene expression levels from post-mortem human brain samples (N=467) reported by the CommonMind Consortium (CMC), we find that conditional eQTL are widespread; 63% of genes with primary eQTL also have conditional eQTL. In addition, genomic features associated with conditional eQTL are consistent with context specific (i.e. tissue, cell type, or developmental time point specific) regulation of gene expression. Integrating the Psychiatric Genomics Consortium schizophrenia (SCZ) GWAS and CMC conditional eQTL data reveals forty loci with strong evidence for co-localization (posterior probability >0.8), including six loci with co-localization of conditional eQTL. Our co-localization analyses support previously reported genes and identify novel genes for schizophrenia risk, and provide specific hypotheses for their functional follow-up. ER -