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Discovery of novel hepatocyte eQTLs in African Americans
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Discovery of novel hepatocyte eQTLs in African Americans
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Journal Article
Discovery of novel hepatocyte eQTLs in African Americans
2020
Overview
African Americans (AAs) are disproportionately affected by metabolic diseases and adverse drug events, with limited publicly available genomic and transcriptomic data to advance the knowledge of the molecular underpinnings or genetic associations to these diseases or drug response phenotypes. To fill this gap, we obtained 60 primary hepatocyte cultures from AA liver donors for genome-wide mapping of expression quantitative trait loci (eQTL) using LAMatrix. We identified 277 eGenes and 19,770 eQTLs, of which 67 eGenes and 7,415 eQTLs are not observed in the Genotype-Tissue Expression Project (GTEx) liver eQTL analysis. Of the eGenes found in GTEx only 25 share the same lead eQTL. These AA-specific eQTLs are less correlated to GTEx eQTLs. in effect sizes and have larger Fst values compared to eQTLs found in both cohorts (overlapping eQTLs). We assessed the overlap between GWAS variants and their tagging variants with AA hepatocyte eQTLs and demonstrated that AA hepatocyte eQTLs can decrease the number of potential causal variants at GWAS loci. Additionally, we identified 75,002 exon QTLs of which 48.8% are not eQTLs in AA hepatocytes. Our analysis provides the first comprehensive characterization of AA hepatocyte eQTLs and highlights the unique discoveries that are made possible due to the increased genetic diversity within the African ancestry genome.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Adaptor Proteins, Signal Transducing - genetics
/ Alternative Splicing - genetics
/ Black or African American - genetics
/ Cytochrome P-450 CYP3A - genetics
/ Datasets
/ Disease
/ Female
/ Genetic Predisposition to Disease
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ Liver
/ Male
/ Medicine
/ Medicine and Health Sciences
/ Nerve Tissue Proteins - genetics
