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Landscape of Conditional eQTL in Dorsolateral Prefrontal Cortex and Co-localization with Schizophrenia GWAS
- Source :
- American Journal of Human Genetics
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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 variants underlie both GWAS and eQTL signals. Most analyses, however, consider only the marginal eQTL signal, rather than dissect this signal into multiple conditionally independent signals 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 (e.g., tissue-, cell type-, or developmental time point-specific) regulation of gene expression. Integrating the 2014 Psychiatric Genomics Consortium schizophrenia (SCZ) GWAS and CMC primary and conditional eQTL data reveals 40 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, identify novel genes associated with schizophrenia risk, and provide specific hypotheses for their functional follow-up.
- Subjects :
- GWAS co-localization
0301 basic medicine
Cells
Quantitative Trait Loci
conditional eQTL
Posterior probability
Prefrontal Cortex
Genome-wide association study
Genomics
Computational biology
Biology
Genome
Article
Epigenesis, Genetic
03 medical and health sciences
Genetic
Genetics
Humans
Gene
Cells, Cultured
Genetics (clinical)
Regulation of gene expression
Cultured
risk gene
Genome, Human
expression quantitative trait loci
eQTLs
neuropsychiatric disorder
gene expression regulation
schizophrenia
030104 developmental biology
complex trait
Conditional independence
fine mapping
Expression quantitative trait loci
Schizophrenia
Genome-Wide Association Study
Epigenesis
Human
Subjects
Details
- ISSN :
- 00029297
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- The American Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....c2195e247d6f51da5e445339e007da95
- Full Text :
- https://doi.org/10.1016/j.ajhg.2018.04.011