# Environmental, Genetic, and Epigenetic Mechanisms for Hormonal Change

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $584,390

## Abstract

Project Summary. Understanding the genetic and environmental regulators of puberty has become a topic of
increasing urgency. Recognizing the importance of the pubertal transition for health across the lifespan,
NIH/NICHD issued PA-18-033, Characterization of the Adolescent Reproductive Transition to solicit
applications for projects that will fill essential gaps in the knowledge base regarding pubertal development,
including increasing our understanding of the “influences of lifestyle factors and environmental exposures.” Our
research aims to identify specific and potentially modifiable environmental factors that influence pubertal
development; we view genetic and epigenetic data as essential tools for accomplishing that goal. Our project
will use data from two independent samples that both combine longitudinal hormonal and epigenetic data with
rich measures of environmental risk. The primary discovery sample will be N = 1000 individuals and their
parents from the Texas Twin Project. We have already collected considerable baseline data on this cohort, and
we will leverage this existing data to build an accelerated longitudinal study spanning adolescence, including a
deep phenotyped sub-sample with up to 8 assessment waves. The replication data set is an existing resource
of N = 214 children recruited in early puberty and re-assessed after a 2-year interval. Together, these unique
datasets will allow us to accomplish three aims. First, we will apply cutting-edge methods in statistical genetics
to findings from previous, well-powered genome-wide association studies (GWAS) of reproductive milestones
in order to (a) develop and validate more powerful polygenic scores that are genome-wide measures of an
individual’s genetic liability toward earlier reproductive development; and (b) probe the extent to which genetic
liabilities operate directly through the individual’s own biology versus through the environment provided by
parents (“genetic nurture”). Second, we will use longitudinal, co-twin-control data on DNA methylation (DNAm)
across the pubertal transition to build a novel epigenetic clock for “pubertal age” and will validate this clock in
an independent replication sample. Developing a molecular biomarker for environmentally-responsive
accelerations in pubertal development has the potential to revolutionize puberty research, just as existing
epigenetic clocks have revolutionized aging research. Third, we will test how established environmental risk
factors for early and accelerated pubertal development (including early life stress, concentrated neighborhood
poverty, and biological father absence) interact with genetic influences using a trio of research designs with
different strengths and limitations – twin, measured gene, and epigenetic designs. Overall, the proposed
research has potential to have very high impact, by providing the scientific community both with empirical
insights regarding the interplay of genetic and environmental regulators ...

## Key facts

- **NIH application ID:** 9980434
- **Project number:** 5R01HD092548-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Kathryn Paige Harden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $584,390
- **Award type:** 5
- **Project period:** 2019-07-18 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980434

## Citation

> US National Institutes of Health, RePORTER application 9980434, Environmental, Genetic, and Epigenetic Mechanisms for Hormonal Change (5R01HD092548-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980434. Licensed CC0.

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