# Systemic interindividual epigenetic variants in African Americans: Identification, characterization, and prospective associations with obesity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $519,638

## Abstract

PROJECT SUMMARY (Abstract)
In addition to genetics and environment, interindividual variation in epigenetic regulation may determine risk of
obesity. Of various epigenetic mechanisms, DNA methylation is this most stable; once established during
development, DNA methylation patterns are mitotically heritable and can persist for many years in humans.
Compared to genetic epidemiology, however, studying epigenetic determinants of obesity is much more
complicated, for two main reasons. First, epigenetic mechanisms are largely cell type-specific, so studying
DNA methylation in easily accessible tissues (like peripheral blood) does not generally provide information
about epigenetic regulation in organs important to energy balance (like the brain). Second, obesity itself can
affect DNA methylation patterns, so `reverse causality' is a problem. Over the last decade we pioneered an
approach to circumvent these obstacles by identifying human genomic regions that exhibit systemic
interindividual variation in DNA methylation (correlated regions of systemic interindividual variation –
CoRSIVs). Last year we reported the identification of nearly 10,000 human CoRSIVs. These regions are stable
and systemic epigenetic variants – essentially epigenetic polymorphisms - enabling large-scale epigenetic
epidemiologic studies using peripheral blood DNA. Our initial screen was conducted in Caucasians, and our
data show that there are many more human CoRSIVs to identify. Given that African Americans are both
grossly underrepresented in genomic and epigenomic analyses, and disproportionately overburdened by
obesity, it is now urgent to scale up and diversify our CoRSIV screen by studying African Americans directly.
Accordingly, our Aims in this project are to 1) Perform an unbiased screen for CoRSIVs in African American
donors in the NIH Gene-Tissue Expression program (GTEx), 2) Validate systemic interindividual epigenetic
variation and cross-tissue prediction of gene expression in a large sample of African Americans, and 3) Test
whether CoRSIV methylation at birth predicts risk of childhood obesity in AA children. We anticipate that
completion of our project will transform the study of epigenetics in human obesity, and epigenetic epidemiology
in general. The focus of this project on African Americans is justified both scientifically and from the basis of
social justice.

## Key facts

- **NIH application ID:** 10272655
- **Project number:** 1R01DK129265-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ROBERT A WATERLAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $519,638
- **Award type:** 1
- **Project period:** 2021-08-24 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10272655

## Citation

> US National Institutes of Health, RePORTER application 10272655, Systemic interindividual epigenetic variants in African Americans: Identification, characterization, and prospective associations with obesity (1R01DK129265-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10272655. Licensed CC0.

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