# Dissecting PCOS Physiology by Defining Phenotypes Associated with PCOS Genetic Risk Factors in Men and Children

> **NIH NIH F32** · BOSTON CHILDREN'S HOSPITAL · 2021 · $74,886

## Abstract

PROJECT SUMMARY/ ABSTRACT
 Polycystic ovarian syndrome (PCOS) is a major health concern that affects up to 10% of all
reproductive-aged women. This complex, heterogeneous condition is often characterized by a triad of
ovulatory dysfunction, hyperandrogenism, and cardiometabolic dysfunction and incurs an estimated $4.3 billion
in annual U.S. healthcare costs. Despite extensive physiologic and genetic studies, the treatment of PCOS
remains limited by an incomplete understanding of the pathophysiology of the disorder. Existing evidence
suggests that PCOS is associated with both ovarian-related factors (gonadotropin secretion and action,
folliculogenesis, androgen biosynthesis) and ovarian-independent factors (adrenal androgen biosynthesis,
insulin secretion and action, weight and energy regulation), but which of these are the inciting events and
which are the secondary consequences are unknown. The overall hypothesis for this study is that PCOS is not
always primarily a disorder of female reproduction, but rather can be primarily a condition of hyperandrogenism
and/or cardiometabolic dysregulation, with ovarian dysfunction as a secondary consequence. To test this
hypothesis, this project will take advantage of a recent genome wide-association study (GWAS) that
discovered numerous genetic variants that influence PCOS risk. Because these genetic variants are present in
all individuals, this discovery provides a unique opportunity to study the phenotypic effects of genetic risk
factors for PCOS in men and prepubertal children without the influence of ovarian factors. This project
leverages the power of the UK Biobank, a population-based cohort of 176,367 unrelated men in the UK, and
two longitudinal pediatric birth cohorts, the Copenhagen Studies on Asthma in Childhood (COPSAC) in
Denmark with 558 children and the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK with
6,791 children. Genetic risk scores (i.e. estimated genetic susceptibility to PCOS) will be calculated in men
from the UK Biobank and prepubertal children from COPSAC and ALSPAC and tested for associations with
hyperandrogenic and cardiometabolic phenotypes. Characterizing the phenotypes in men and children who
carry genetic risk factors for PCOS will provide a starting point for identifying specific biological pathways
underlying the pathogenesis of PCOS, allow for the future development of targeted therapies for PCOS, and
deepen our understanding of pediatric manifestations of genetic risk factors for PCOS.
 The fellowship training plan consists of a co-mentoring team composed of Dr. Joel Hirschhorn and Dr.
Yee-Ming Chan at the Broad Institute and the Division of Endocrinology at Boston Children’s Hospital (BCH).
Dr. Hirschhorn’s lab and the Broad Institute will provide Dr. Zhu with extensive training in human genetics of
polygenic disease and computational biology and bioinformatics. Dr. Chan’s lab will provide Dr. Zhu with
training in scientific and clinical pediatric...

## Key facts

- **NIH application ID:** 10230375
- **Project number:** 1F32HD103317-01A1
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Jia Zhu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $74,886
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230375

## Citation

> US National Institutes of Health, RePORTER application 10230375, Dissecting PCOS Physiology by Defining Phenotypes Associated with PCOS Genetic Risk Factors in Men and Children (1F32HD103317-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10230375. Licensed CC0.

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