B4329 - Identifying Genetic and Non-Genetic Factors that Influence Age at Menarche - 24/05/2023

B number: 
Principal applicant name: 
Yee-Ming Chan | Boston Children's Hospital (United States)
Title of project: 
Identifying Genetic and Non-Genetic Factors that Influence Age at Menarche
Proposal summary: 

This projects seeks to deepen our understanding of how the timing of puberty affects adult health outcomes, specifically, risk of cardiovascular disease (CVD). The age at which a girl gets her first menstrual period (age at menarche, or AAM) has a peculiar relationship with CVD: both earlier and later AAM are associated with increased risk of CVD in adulthood.

In preliminary work focusing on later AAM, we applied human genetic techniques to distinguish the effects of common genetic changes on AAM from the effects of other, yet-to-be-identified factors. We were surprised to find that the relationship between later AAM and CVD depends on the underlying cause of later AAM. If caused by common genetic changes, later AAM is actually associated with _lower_ risk of cardiovascular disease. In contrast, if caused by other factors, later AAM is associated with _increased_ risk of cardiovascular disease.

The broad goals of this project are 1) to better understand how common genetic changes affect AAM by subgrouping common genetic variants based on their effects on childhood factors known to affect AAM, and 2) to identify factors other than common genetic changes that influence AAM.

Impact of research: 
1) A fuller understanding of factors that affect pubertal timing, which is currently poorly understood 2) Improved tools to understand the complex relationship between pubertal timing and cardiovascular disease in adulthood, with the ultimate goal of identifying modifiable factors that could be targeted to improve adult health.
Date proposal received: 
Wednesday, 10 May, 2023
Date proposal approved: 
Wednesday, 24 May, 2023
Endocrinology, Puberty, Statistical methods, Polygenic risk score analyses, BMI, Cardiovascular, Genetic epidemiology, Genetics, Genomics, Puberty