# Early life environmental effects: molecular mechanisms and inter-individual variation

> **NIH NIH R35** · VANDERBILT UNIVERSITY · 2022 · $396,250

## Abstract

Project Summary
Early life environments can have profound and long-lasting effects on human health, yet the mechanistic basis
of these effects remain poorly understood as do the factors that explain inter-individual variation. These gaps in
knowledge severely limit our ability to both predict susceptible individuals and to develop effective intervention
strategies. At the molecular level, early life effects on later life health are thought to be mediated by stable
changes in gene regulation. However, many gene regulatory elements are responsive to environmental stimuli
throughout life, making it challenging to isolate the effects of early life conditions or to understand their stability,
especially when within-lifetime environmental variation is absent or longitudinal data are not available. My
research program aims to overcome these challenges by working with two subsistence-level groups: 1) the
Turkana of Kenya, who are experiencing rapid lifestyle change such that early life and adult conditions are largely
decoupled and 2) the Tsimane of Bolivia, who have been followed longitudinally for decades. In both groups, I
will generate genome-wide gene regulatory datasets (DNA methylation, gene expression) paired with information
on environmental experiences and health, allowing me to identify the mechanisms that embed early life
exposures into lifelong physiology. I will also generate genome-wide genotype data for each individual, in order
to ask whether genetic variation predicts sensitivity versus resilience to early life challenges at the gene
regulatory level. Finally, I will complement this field-based, observational work with lab-based methods capable
of testing for causal connections between 1) DNA methylation and gene expression and 2) genotype and
environmentally-induced gene expression, both in high-throughput. In doing so, this project will uncover the gene
regulatory mechanisms that mediate early life effects on health, as well as the degree to which these
relationships are modified by genetic variation. By working “in the field” and “in the lab”, the proposed work will
inform our understanding of developmental and environmental processes in natural human populations as well
as causal mechanisms. More broadly, the proposed projects will link a major global phenomenon—increasing
urbanization and market-integration—with gene regulatory processes and health in two understudied and
underserved populations (Africans and Amerindians). It will also generate new methods and resources that will
inform our understanding of the general patterns of genotype x environment interactions in human complex traits.

## Key facts

- **NIH application ID:** 10499757
- **Project number:** 1R35GM147267-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Amanda Lea
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,250
- **Award type:** 1
- **Project period:** 2022-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499757

## Citation

> US National Institutes of Health, RePORTER application 10499757, Early life environmental effects: molecular mechanisms and inter-individual variation (1R35GM147267-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499757. Licensed CC0.

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