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dc.contributor.authorPark, CS
dc.contributor.authorDe, T
dc.contributor.authorXu, Y
dc.contributor.authorZhong, Y
dc.contributor.authorSmithberger, E
dc.contributor.authorAlarcon, C
dc.contributor.authorGamazon, ER
dc.contributor.authorPerera, MA
dc.date.accessioned2020-11-24T16:22:13Z
dc.date.available2020-11-24T16:22:13Z
dc.date.issued2019
dc.date.submitted2019-03-11
dc.identifier.issn2056-7944
dc.identifier.others41525-019-0102-y
dc.identifier.other102
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/313270
dc.description.abstractAfrican Americans (AAs) are an admixed population with widely varying proportion of West African ancestry (WAA). Here we report the correlation of WAA to gene expression and DNA methylation in AA-derived hepatocytes, a cell type important in disease and drug response. We perform mediation analysis to test whether methylation is a mediator of the effect of ancestry on expression. GTEx samples and a second cohort are used as validation. One hundred and thirty-one genes are associated with WAA (FDR < 0.10), 28 of which replicate and represent 220 GWAS phenotypes. Among PharmGKB pharmacogenes, VDR, PTGIS, ALDH1A1, CYP2C19, and P2RY1 nominally associate with WAA (p < 0.05). We find 1037 WAA-associated, differentially methylated regions (FDR < 0.05), with hypomethylated genes enriched in drug-response pathways. In conclusion, WAA contributes to variability in hepatocyte expression and DNA methylation with identified genes previously implicated for diseases disproportionately affecting AAs, including cardiovascular (PTGIS, PLAT) and renal (APOL1) disease, and drug response (CYP2C19).
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectArticle
dc.subject/631/208/199
dc.subject/631/208/457
dc.subjectarticle
dc.titleHepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.
dc.typeArticle
dc.date.updated2020-11-24T16:22:12Z
prism.issueIdentifier1
prism.publicationNameNPJ Genom Med
prism.volume4
dc.identifier.doi10.17863/CAM.60375
dcterms.dateAccepted2019-09-27
rioxxterms.versionofrecord10.1038/s41525-019-0102-y
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidPark, CS [0000-0003-0378-507X]
dc.contributor.orcidPerera, MA [0000-0002-1146-2791]
dc.identifier.eissn2056-7944
pubs.funder-project-idU.S. Department of Health & Human Services | NIH | National Institute on Minority Health and Health Disparities (NIMHD) (1R01MD009217-01)
cam.issuedOnline2019-11-25


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)