B4620 - Effects of Maternal Genetic Risk Factors for Polycystic Ovary Syndrome on Birth and Childhood Outcomes in Offspring - 17/05/2024

B number: 
Principal applicant name: 
Jia Zhu | Boston Children's Hospital, Harvard Medical School (USA)
Dr. Joel N. Hirschhorn, Dr. Yee-Ming Chan
Title of project: 
Effects of Maternal Genetic Risk Factors for Polycystic Ovary Syndrome on Birth and Childhood Outcomes in Offspring
Proposal summary: 

*Please note this new proposal will re-use the dataset that has been provided for the previous project ID B3581.*

Polycystic ovary syndrome (PCOS) is a major health concern that affects up to 10% of reproductive-aged women and is the leading cause of female infertility. This complex, heterogenous condition is characterized by ovulatory dysfunction and hyperandrogenism and is often associated with metabolic dysregulation and increased risk for adverse birth outcomes. Existing evidence suggests that the androgenic and metabolic features of PCOS can be passed down from mothers to their offspring, but the relative contributions of maternal genetics and intrauterine environmental factors to these features in offspring are not known.

Our original project ID B3581 studies metabolic and growth and developmental phenotypes in children that may be associated with PCOS. We have recently identified that a higher polygenic risk score (PRS) for PCOS is associated with higher BMI, fat-mass index, and risk of obesity in childhood and earlier age at pubarche and younger age at peak height velocity. These associations persisted after controlling for the maternal PCOS polygenic risk score, indicating that genetic risk for PCOS has direct effects in offspring. In addition, genetic risk for PCOS could also have indirect effects in children through direct effects on the intrauterine environment in their mothers. For example, mothers with PCOS have an increased risk of preterm delivery, attributed to metabolic perinatal complications, such as pre-eclampsia.

I hypothesize that maternal PCOS genetic factors and associated intrauterine environmental factors play an integral role in the development of adverse birth outcomes and childhood androgenic and metabolic features of PCOS in offspring.

Impact of research: 
Our project will provide insights into the interplay between PCOS genetics and intrauterine environment and the resulting adverse effects on maternal and child health, and thereby, pave the way for a targeted approach to the preventative treatment of PCOS, and its associated conditions in mothers and children.
Date proposal received: 
Friday, 17 May, 2024
Date proposal approved: 
Friday, 17 May, 2024
Endocrinology, Diabetes, Fertility/infertility, Obesity, Pregnancy - e.g. reproductive health, postnatal depression, birth outcomes, etc., Computer simulations/modelling/algorithms, Statistical methods, Biomarkers - e.g. cotinine, fatty acids, haemoglobin, etc., Birth outcomes, BMI, Cardiovascular, Genetics, Genomics, Offspring, Sex differences