Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Racial Disparities in Epigenetic Aging of the Right vs Left Colon.

ABSTRACT: There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared to individual-matched left colon (1.51 years; 95% CI = 0.62 to 2.40 years; two-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; two-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.

SUBMITTER: Devall M

PROVIDER: S-EPMC8634501 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Racial Disparities in Epigenetic Aging of the Right versus the Left Colon

Project description:Here, we present the first study showing race and side-specific differences in the trajectories of epigenetic aging in normal colonic mucosa. The cohort conisted of matched biopsies of left/right colon from healthy individuals (n=129). The majority of individuals were African American (n=89). Methylation arrays (Illumina EPIC) were performed on DNA extracted from fresh frozen biopsies taken at the time of colonoscopy. Our results provide novel insight of epigenetic aging underlying racial disparities in CRC. Side-specific colonic epigenetic aging may be a promising marker to guide interventions to reduce CRC burden.

2020-10-16 | GSE151732 | GEO

Racial Disparities in Epigenetic Aging of the Right versus the Left Colon

Project description:Racial Disparities in Epigenetic Aging of the Right versus the Left Colon

| PRJNA637075 | ENA

The role of epigenetic aging in education and racial/ethnic mortality disparities among older U.S. Women.

Project description:BackgroundHigher mortality experienced by socially disadvantaged groups and/or racial/ethnic minorities is hypothesized to be, at least in part, due to an acceleration of the aging process. Using a new epigenetic aging measure, Levine DNAmAge, this study aimed to investigate whether epigenetic aging accounts for mortality disparities by race/ethnicity and education in a sample of U.S. postmenopausal women.Methods1834 participants from an ancillary study (BA23) in the Women's Health Initiative, a national study that recruited postmenopausal women (50-79 years) were included. Over the 22 years of follow-up, 551 women died, and 31,946 person-years were observed. Levine DNAmAge (unit in years) was calculated based on an equation that we previously developed in an independent sample, which incorporates methylation levels at 513 CpG sites.ResultsAs previously reported, non-Hispanic blacks and Hispanics were epigenetically older than non-Hispanic whites of the same chronological age. Similarly, those with less education had older epigenetic ages than expected in the full sample, as well as among non-Hispanic whites and Hispanics, but not among non-Hispanic blacks. Non-Hispanic blacks and those with low education exhibited the greatest risk of mortality. However, this association was partially attenuated when accounting for differences in DNAmAge. Furthermore, formal mediation analysis suggested that DNAmAge partially mediated the mortality increase among non-Hispanic blacks, compared to non-Hispanic whites (proportion mediated, 15.8%, P = 0.002), as well as the mortality increase for those with less than high school education, compared to college educated (proportion mediated, 11.6%, P < 2E-16).ConclusionsAmong a group of postmenopausal women, non-Hispanic blacks and those with less education exhibit higher epigenetic aging, which partially accounts for their shorter life expectancies.

| S-EPMC6555423 | biostudies-literature

Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence.

Project description:Marginalization due to structural racism may confer an increased risk for aging-related diseases - in part - via effects on people's mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.

| S-EPMC10996608 | biostudies-literature

Colonic Crohn's left and right colon

Project description:Colonic Crohn's left and right colon

| PRJNA593867 | ENA

Epigenetic age and socioeconomic status contribute to racial disparities in cognitive and functional aging between Black and White older Americans.

Project description:Epigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.

| S-EPMC10592997 | biostudies-literature

When left does not seem right: epigenetic and bioelectric differences between left- and right-sided breast cancer.

Project description:BackgroundDuring embryogenesis lateral symmetry is broken, giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms.MethodsWe performed in-silico analyses on breast tumors of public datasets, developed xenografted tumors, and conditioned MDA-MB-231 cells with L/R mammary extracts.ResultsWe found L/R differential DNA methylation involved in embryogenic and neuron-like functions. Focusing on ion-channels, we discovered significant L/R epigenetic and bioelectric differences. Specifically, L-sided cells presented increased methylation of hyperpolarizing ion channel genes and increased Ca2+ concentration and depolarized membrane potential, compared to R-ones. Functional consequences were associated with increased proliferation in left tumors, assessed by KI67 expression and mitotic count.ConclusionsOur findings reveal considerable L/R asymmetry in cancer processes, and suggest specific L/R epigenetic and bioelectric differences as future targets for cancer therapeutic approaches in the breast and many other paired organs.

| S-EPMC8817536 | biostudies-literature

Colonic Crohn's left and right colon

Project description:Colonic Crohn's Disease from a single patient in remission with mild disease index

2020-08-24 | GSE141553 | GEO

Epigenetic regulation of left-right asymmetry by DNA methylation.

Project description:DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left-right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of DNA methyltransferase 1 (dnmt1) or dnmt3bb.1 in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning. Knockdown of dnmt1 in Xenopus embryos also causes similar defects. Mechanistically, loss of dnmt1 function induces hypomethylation of the lefty2 gene enhancer and promotes lefty2 expression, which consequently represses Nodal signaling in zebrafish embryos. We also show that Dnmt3bb.1 regulates collective DFC migration through cadherin 1 (Cdh1). Taken together, our data uncover dynamic DNA methylation as an epigenetic mechanism to control LR determination during early embryogenesis in vertebrates.

| S-EPMC5641680 | biostudies-literature

Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers.

Project description:Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials.

| S-EPMC5689690 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data