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Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE124076 | GEO | 2019/10/31

REPOSITORIES: GEO

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Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [Methylation]

Project description:In African Americans (AA), the proportion of West African ancestry (WAA) may explain the genetic drivers of health disparities in disease. Analysis of RNA sequencing data from sixty AA-derived primary hepatocytes identified 32 gene expression profiles associated with WAA (FDR <0.05) with enrichment in angiogenesis and inflammatory pathways (FDR <0.1). Association of DNA methylation to WAA identified 1037 differentially methylated regions (FDR <0.05), with hypomethylated genes enriched for drug response pathways. Within the PharmGKB pharmacogene, VDR, PTGIS, ALDH1A1, CYP2C19 and P2RY1 were associated with WAA (p <0.05) with replication of CYP2C19 and VDR in the GTEx liver cohort. For every 1% increment in WAA, P2RY1 gene expression increased by 1.6% and CYP2C19 gene expression decreased by 1.4%, suggesting effects on clopidogrel response and platelet aggregation. We conclude that WAA contributes to variablity in hepatic gene expression and DNA methylation with identified genes indicative of health disparities prevalent in AAs.

2019-10-31 | GSE123995 | GEO

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

2023-01-10 | GSE222593 | GEO

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

2019-10-31 | GSE124074 | GEO

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans

Project description:Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans

| PRJNA510661 | ENA

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [Methylation]

Project description:Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [Methylation]

| PRJNA510602 | ENA

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

Project description:Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

| PRJNA922591 | ENA

Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

Project description:Uncovering the role admixture in health disparities: Association of hepatocyte gene expression and DNA methylation to African Ancestry in African-Americans [RNA-seq]

| PRJNA510660 | ENA

African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.

Project description:PurposeTo examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D).MethodsBetween 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software.ResultsIn the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1.ConclusionsIn this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.

| S-EPMC4477259 | biostudies-literature

Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.

Project description:African 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).

| S-EPMC6877651 | biostudies-literature

A genome-wide admixture scan for ancestry-linked genes predisposing to sarcoidosis in African-Americans.

Project description:Genome-wide linkage and association studies have uncovered variants associated with sarcoidosis, a multiorgan granulomatous inflammatory disease. African ancestry may influence disease pathogenesis, as African-Americans are more commonly affected by sarcoidosis. Therefore, we conducted the first sarcoidosis genome-wide ancestry scan using a map of 1384 highly ancestry-informative single-nucleotide polymorphisms genotyped on 1357 sarcoidosis cases and 703 unaffected controls self-identified as African-American. The most significant ancestry association was at marker rs11966463 on chromosome 6p22.3 (ancestry association risk ratio (aRR)=1.90; P=0.0002). When we restricted the analysis to biopsy-confirmed cases, the aRR for this marker increased to 2.01; P=0.00007. Among the eight other markers that demonstrated suggestive ancestry associations with sarcoidosis were rs1462906 on chromosome 8p12, which had the most significant association with European ancestry (aRR=0.65; P=0.002), and markers on chromosomes 5p13 (aRR=1.46; P=0.005) and 5q31 (aRR=0.67; P=0.005), which correspond to regions we previously identified through sib-pair linkage analyses. Overall, the most significant ancestry association for Scadding stage IV cases was to marker rs7919137 on chromosome 10p11.22 (aRR=0.27; P=2 × 10(-5)), a region not associated with disease susceptibility. In summary, through admixture mapping of sarcoidosis we have confirmed previous genetic linkages and identified several novel putative candidate loci for sarcoidosis.

| S-EPMC3058725 | biostudies-literature

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