Discovery of novel hepatocyte eQTLs in African Americans

Autoři: Yizhen Zhong aff001;  Tanima De aff001;  Cristina Alarcon aff001;  C. Sehwan Park aff001;  Bianca Lec aff001;  Minoli A. Perera aff001
Působiště autorů: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America aff001
Vyšlo v časopise: Discovery of novel hepatocyte eQTLs in African Americans. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008662
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008662


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.

Klíčová slova:

Europe – Exon mapping – Gene expression – Gene mapping – Gene regulation – Genome-wide association studies – Hepatocytes – Quantitative trait loci


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