# DNA methylation & adversity: pathways from exposures to health inequities

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 · $542,971

## Abstract

Project Summary
Addressing the objective of PAR-16-355 to “expand approaches for understanding epigenetic mechanisms
by which social factors lead to biological changes that affect health disparities,” our study will conduct novel
population-based discovery and replication analyses to investigate how DNA methylation (DNAm) varies
with exposure to racial discrimination, economic hardship, and air pollution, and implications for disparities
in cardiometabolic disease risk and accelerated aging (defined as epigenetic age > chronological age).
For the discovery phase, we will newly obtain DNAm from the stored blood spots of our My Body, My Story
(MBMS) study (R01 AG027122), whose participants comprise a random sample of 1005 US-born non-
Hispanic black (n = 504) and non-Hispanic white (n = 501) adults, aged 35 to 64 years, recruited from four
community health centers in Boston, MA (2008-2010). This study has rich data on: (a) racial discrimination
and socioeconomic position, each measured at multiple levels and across the life-course, plus residential air
pollution in the past year; (b) cardiometabolic outcomes; and (c) relevant covariates. For replication, we will
use the newly available analogous DNAm, exposure, and health data from a subset of Wave 5 (2010-2012)
participants in the Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1264, age 55-94; 582 non-Hispanic
white, 270 non-Hispanic black; 404 Hispanic, from Baltimore, MD, Forsyth County, NC, NYC, NY, and St.
Paul, MN). To strengthen causal inference based on the cross-sectional data, we will employ MR-Base, a
recently constructed highly powerful application that harnesses publicly-available genome-wide association
study (GWAS) summary data and Mendelian Randomization (MR) to assess causal directions of associa-
tions between exposures, DNAm, and health outcomes. Our Specific Aims thus are:
Aim 1: Conduct novel analyses to identify variation in DNAm associated with: (1) Aim 1.1: exposure to
racial discrimination, economic hardship, and air pollution; and (2) Aim 1.2: measured cardiometabolic
outcomes (blood pressure, fasting insulin, Type 2 diabetes, Framingham Cardiovascular Disease 10-year
risk score, metabolic syndrome); plus (3) Aim 1.3: For DNAm-health outcome associations observed in Aim
1.2, use MR-Base to strengthen causal inference about the direction of the associations (e.g., methylation
causes vs. is due to disease); discovery analyses: MBMS; replication analyses: MESA.
Aim 2: Assess the relationships between both the Aim 1 study exposures and health outcomes with
accelerated aging (epigenetic age > chronological age), as identified by three newly identified DNAm
“clocks” (Horvath, Hannum, and DNAm PhenoAge); discovery: MBMS; replication: MESA.
Aim 3: Analyze if the methylation sites and “clocks” associated with both the study exposures and health
outcomes mediate these exposure-outcomes associations, thereby contributing to health inequities.
Impact: Results will advance knowledge...

## Key facts

- **NIH application ID:** 10129214
- **Project number:** 5R01MD014304-03
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** NANCY KRIEGER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $542,971
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129214

## Citation

> US National Institutes of Health, RePORTER application 10129214, DNA methylation & adversity: pathways from exposures to health inequities (5R01MD014304-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10129214. Licensed CC0.

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