Evidence map›Paper›PMID 40205465›Full record

ArticleClinical epigenetics2025

Influence of race, ethnicity, and sex on the performance of epigenetic predictors of phenotypic traits.

Dennis Khodasevich, Nicole Gladish, Saher Daredia, Anne K Bozack, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Belinda L Needham, David H Rehkopf, Andres Cardenas

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In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Review
  2. Article
  3. Observational
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Dennis KhodasevichDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA.
Nicole GladishDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA.
Saher DarediaDivision of Epidemiology, Berkeley Public Health, University of California, Berkeley, Berkeley, CA, USA.
Anne K BozackDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA.
Hanyang ShenDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA.
Jamaji C Nwanaji-EnweremDepartment of Emergency Medicine, Center for Health Justice, and Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Belinda L NeedhamDepartment of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
David H RehkopfDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA.
Andres CardenasDepartment of Epidemiology and Population Health, Stanford University, Palo Alto, CA, 94305, USA. andresca@stanford.edu.

Funding

Race/Ethnicity, DNA Methylation, and Disparities in Cardiovascular Mortality: NHANES 1999-2002R01MD011721 · NIMHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI NEEDHAM, BELINDA L., REHKOPF, DAVID H · 2017 to 2021
$3.1M
Common and Distinct Influences of Prenatal and Postnatal Early-Life Adversity on Epigenomic Trajectories in Mexican American ChildrenR01MD016595 · NIMHD · UNIVERSITY OF CALIFORNIA BERKELEY · PI Andres Cardenas, Julianna Deardorff · 2022 to 2026
$3.0M
PRENATAL AND POSTNATAL EXPOSURE TO ENVIRONMENTAL MIXTURES: NEURODEVELOPMENT AND DNA METHYLATION BIOMARKERSR01ES031259 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CARDENAS, ANDRES · 2020 to 2024
$1.9M
Early life influences on Epigenetic Aging in Mexican-American childrenR03AG067064 · NIA · UNIVERSITY OF CALIFORNIA BERKELEY · PI HOLLAND, NINA T · 2020 to 2021
$159k
NIA NIH HHS R03 AG067064NIEHS NIH HHS R01 ES031259NIMHD NIH HHS R01 MD011721NIMHD NIH HHS R01 MD016595
6 · The paper itself

Abstract

backgroundDNA methylation-based predictors of phenotypic traits including leukocyte proportions, smoking activity, biological aging, and circulating levels of plasma proteins are widely used as biomarkers in public health research. However, limited racial and ethnic diversity of research participants is an ongoing issue for epigenetics research, and the potential downstream impacts of limited diversity in training samples on the performance of epigenetic predictors remains poorly understood. We examined the performance of epigenetic predictors of chronological age (also known as epigenetic clocks), telomere length, cell proportions, and plasma proteins within a diverse sample of adult NHANES participants during the 1999-2000 and 2001-2002 survey cycles, both overall and stratified by self-reported race/ethnicity and sex. We utilized correlation coefficients and median absolute errors (MAE) to judge predictor performance, and bootstrapping and multivariate regression to assess the significance of differences between groups.

resultsAll epigenetic predictors were significantly associated with their corresponding phenotypic traits in the overall population, with particularly high correlations for the epigenetic clocks and cell proportion estimates. Several significant differences in performance were observed between racial/ethnic groups, particularly for the plasma protein predictors, with a reoccurring trend of lower correlation in Mexican American and non-Hispanic Black participants compared to non-Hispanic White participants. Sex-differences in performance for several predictors were also identified but were not as pronounced. Multivariate regression models indicated that disparities in epigenetic predictor performance persisted after accounting for overall differences in epigenetic predictions related to race/ethnicity and sex, as well as further adjustment for estimated cell proportions and SES variables.

conclusionsWe found evidence for substantial disparities in epigenetic predictor performance, with each predictor exhibiting at least one significant difference in correlation or MAE related to race, ethnicity, or sex.

Indexed as

Epigenesis, GeneticEpigenomicsEthnicityRacial GroupsAdultAgedAgingBlack or African AmericanDNA MethylationFemaleHumansMaleMexican AmericansMiddle AgedNutrition SurveysPhenotypeAgingDisparitiesEpigeneticsMachine learning

Identifiers

PMID40205465
PMCPMC11983795

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.