# Integrated analysis of genetic and epigenetic variants in central precocious puberty

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $223,750

## Abstract

Abstract:
The hypothalamic-pituitary-gonadal (HPG) axis regulates the timing of pubertal onset. Premature re-activation
of gonadotropin-releasing hormone (GnRH) secretion in childhood leads to development of central precocious
puberty (CPP). CPP, in addition to conferring behavioral and psychiatric disorders, is associated with increased
risk of cardiovascular and cardiometabolic disease, obesity, diabetes, and cancer in adulthood. Therefore, there
is a dire need to identify the pathways that are involved in early re-activation of the HPG axis to better diagnose
and treat this disorder. Studies have identified the central roles of KISS1 and KISS1R in activation of the HPG
axis. More recently, we have identified mutations in the imprinted genes, MKRN3 and DLK1, in familial CPP,
suggesting that both genetic and epigenetic alterations regulate the timing of puberty. We now propose to use a
population genetics approach to perform an integrated analysis of genetic and epigenetic variants to identify new
underlying causes for CPP in individuals with no known causes. The objective of our study is to investigate the
association between copy number variants and DNA methylation in patients with idiopathic CPP. We will address
this objective in two aims: 1) perform association analysis between genetic alterations and DNA methylation in
a cohort of patients with CPP; and 2) validate the associations identified using a second cohort of patients and
further determine if the regions associated with DNA methylation are enriched for regulatory elements as defined
by the Encyclopedia of DNA Elements (ENCODE) consortium. This proposed analysis will help to delineate
correlated genetic and epigenetic alterations underlying CPP. The results will aid in the development of new
diagnostic strategies for CPP and facilitate timely intervention and treatment to improve the health and quality of
life for these children.

## Key facts

- **NIH application ID:** 10131232
- **Project number:** 5R21HD098684-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Ursula B. Kaiser
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,750
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131232

## Citation

> US National Institutes of Health, RePORTER application 10131232, Integrated analysis of genetic and epigenetic variants in central precocious puberty (5R21HD098684-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131232. Licensed CC0.

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