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Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (RNA-seq)

ABSTRACT: African Americans (AA) are 70% more likely than Caucasian Americans (CA) to die from heart failure (HF) even after adjusting for known causes. Although the causal factors responsible for this racial disparity remain unknown, it is theorized that environmental stressors This alarming health disparity represents an important challenge to U.S. healthcare as global prevalence of heart failure has already exceeded epidemic levels with a disease burden that disproportionately impacts members of ethnic and racial minorities. The current multicohort study of cardiac DNA methylation identifies the cardiac epigenome as a previously unrecognized syntax that encodes race-based environmental differences in the failing human heart.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164196 | GEO | 2021/03/11

REPOSITORIES: GEO

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Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (MethylationEPIC array)

Project description:African Americans (AA) are 70% more likely than Caucasian Americans (CA) to die from heart failure (HF) even after adjusting for known causes. Although the causal factors responsible for this racial disparity remain unknown, it is theorized that environmental stressors This alarming health disparity represents an important challenge to U.S. healthcare as global prevalence of heart failure has already exceeded epidemic levels with a disease burden that disproportionately impacts members of ethnic and racial minorities. The current multicohort study of cardiac DNA methylation identifies the cardiac epigenome as a previously unrecognized syntax that encodes race-based environmental differences in the failing human heart.

2021-03-11 | GSE164195 | GEO

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure

Project description:Heart Failure (HF) is a multifactorial syndrome and that remains a leading cause of worldwide morbidity. Despite its high prevalence, only half 50% of HF patients respond to guideline-directed medical management, prompting therapeutic efforts . Therapeutic avenues are forced to confront the molecular underpinnings of its heterogeneity of HF as a clinical syndrome to identify novel molecular targets. In both pilot (n = 11) and testing (n = 31) cohorts (n = 31), unsupervised multidimensional scaling of genome-wide myocardial DNA methylation exhibited a bimodal distribution of CpG methylation found largely to occur in the promoter regions of metabolic genes.. Among the available patient attributes, only categorical patient race could delineate this methylation signature, with African American (AA) and Caucasian American (CA) samples clustering separately. Because race is a social construct, and thus a poor proxy of human physiology, extensive review of medical records was conducted, but ultimately failed to identify co-variates of race at the time of LVAD surgery. By contrast, retrospective analysis exposed a higher all-cause mortality among AA (56.3%) relative to CA (16.7%) patients at 2 years following LVAD placement (P = 0.03). .G To mitigate concerns of genetic confounding factors, putative single-nucleotide polymorphisms (SNPs) were identified by proximity to CpG methylation sites. Nevertheless, a minor proportion of SNPs (0.15%) was identified, and no evidence of racial dissimilarity was seen among them. By contrast, geocoding-based approximation of patient demographics uncovered disparities in income levels among AA relative to CA patients. Therefore, Although although additional studies studies are warrantedneeded, our multicohort studythe current analysis implicates identifies cardiac DNA methylation as as a previously unrecognized indicator of socioeconomic disparity in human heart failure outcomes.

2021-03-11 | GSE164197 | GEO

Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure

Project description:Racial and Socioeconomic Disparity Associates with Differences in Cardiac DNA Methylation among Men with End-Stage Heart Failure

| PRJNA689539 | ENA

Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (RNA-seq)

Project description:Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (RNA-seq)

| PRJNA689544 | ENA

Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (MethylationEPIC array)

Project description:Cardiac DNA Methylation Underlies Racial and Socioeconomic Disparities among Patients with End-Stage Heart Failure (MethylationEPIC array)

| PRJNA689545 | ENA

First characterization of the transcriptome of lung fibroblasts of SSc patients and healthy donors of African ancestry.

Project description:Systemic sclerosis (SSc) is a rare and devastating connective tissue disorder that results in fibrosis and vascular abnormalities that affect the skin and visceral organs, and SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death amongst SSc patients. Racial disparity is noticeable in SSc as African Americans (AA) have a higher frequency and severity of diseases than European Americans (EA). Using RNAseq, we determined differentially expressed genes (DEGs) in primary pulmonary fibroblasts (pFBs) outgrown from SSc-PF lungs (SScL) and normal lungs (NL) of AA and EA patients to characterize the unique transcriptomic signatures of AA-NL and AA-SScL pFBs by performing a systems level analysis. We identified 69 DEGs in “AA-NL vs. EA-NL” and 384 DEGs in “AA-SScL vs. EA-SScL” comparisons, and only 7.5% DEGs were commonly deregulated in the “SScL vs. NL in AA and EA” disease mechanisms comparison. Surprisingly, we also identified a disease-like signature in AA-NL pFBs. Our data highlight that the transcriptome of AA pFBs is unique and may hold the key to understanding racial disparity in SSc-PF, the first step in developing efficacious therapeutic strategies.

2023-03-01 | GSE215841 | GEO

Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [miRNA-Seq]

Project description:We evaluate the epigenetic mechanisms of racial disparity in HCC through an integrated analysis of DNA methylation, miRNA, and combined regulation of gene expression. Specifically, we acquired DNA methylation, mRNA-seq, and miRNA-seq data through the analysis of tumor and adjacent normal liver tissues from African Americans (AA) and European Americans (EA) with HCC. Results: Using mixed ANOVA, we identified cytosine-phosphate-guanine (CpG) sites, mRNAs, and miRNAs that are statistically significantly altered in HCC vs. adjacent normal in a race-specific manner. Through integrative analysis, we identified significantly differentially expressed genes in HCC with disparate epigenetic regulation, associated with changes in miRNA expression for AA and DNA methylation for EA.

2021-09-29 | GSE176288 | GEO

Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [DNA-Methylation]

2021-09-29 | GSE176273 | GEO

Integrative analysis of DNA methylation and microRNA expression reveals mechanisms of disparity in hepatocellular carcinoma [RNA-Seq]

2021-09-29 | GSE176271 | GEO

Molecular Dysregulation Underlying Racial Disparity in Hepatocellular Carcinoma (HCC)

Project description:Hepatocellular carcinoma (HCC) is a highly fatal disease with mortality running parallel to its incidence. For HCC patients, there is a statistically significant increase in incidence and mortality and a decrease in 5-year survival rates in African American (AA)/Black patients compared to non-Hispanic (white) patients. There is a gap of knowledge in our understanding of the molecular mechanism underlying the HCC racial disparity between AA/Black and white patients. To address this issue, we analyzed existing RNA-sequencing (RNA-seq) data from HCC patients in the TCGA database, and performed RNA-seq in 14 white and 19 AA/Black HCC patients from Virginia Commonwealth University. In both analysis the only pathway which showed statistically significant activation in AA/Black patients, compared to white patients, was type I interferon (IFN-I) signaling. A four gene signature of IFN-I-stimulated genes (ISGs) showed increased expression in AA/Black HCC tumors compared to their white counterparts. HCC is a disease of chronic inflammation and IFN-I function as a pro-inflammatory and immunosuppressive cytokine. These findings suggest a potential role of IFN-I in conferring disparity in AA/Black HCC patients.

2023-09-15 | GSE223795 | GEO

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