# Epigenetic variation at metastable epialleles: Effects on human obesity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $369,507

## Abstract

PROJECT SUMMARY (Abstract)
In addition to genetics and environment, interindividual variation in epigenetic regulation may determine risk of
obesity. Exceptional genomic loci called metastable epialleles offer unprecedented opportunities to test this.
Metastable epialleles – essentially epigenetic polymorphisms – exhibit interindividual variation in DNA
methylation that is neither tissue-specific nor genetically mediated. Establishment of DNA methylation at these
loci is influenced by periconceptional environment, providing a potential explanation for how environmental
influences during development increase risk of obesity later in life (developmental programming). We have
shown that DNA methylation profiling across multiple tissues from multiple individuals is an effective approach
to discover metastable epialleles, and have already identified several implicated in obesity. To test the overall
hypothesis that individual differences in DNA methylation at human metastable epialleles predict risk of adult
weight gain, we will partner with the NIH Genotype-Tissue Expression (GTEx) program and the Starr County
Health Studies to pursue the following Specific Aims: Aim 1 - Screen for candidate metastable epialleles in 3
tissues from each of 10 GTEx donors. Aim 2 - Validate bona-fide metastable epialleles by studying 8 tissues
from each of 100 GTEx donors. Aim 3 - Test whether DNA methylation at metastable epialleles affects risk of
subsequent weight gain.
This translational project will both discover new human MEs associated with obesity, and prospectively test
whether these epigenetic variants are stable through adulthood, and affect risk of subsequent weight gain.
Hence, the proposed research will provide crucial insights into how interindividual epigenetic variation affects
risk of obesity.

## Key facts

- **NIH application ID:** 9878841
- **Project number:** 5R01DK111522-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** CRISTIAN COARFA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $369,507
- **Award type:** 5
- **Project period:** 2017-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878841

## Citation

> US National Institutes of Health, RePORTER application 9878841, Epigenetic variation at metastable epialleles: Effects on human obesity (5R01DK111522-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9878841. Licensed CC0.

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