Early Life Determinants of Metabolic and Reproductive Health
type: CreativeWork
description: Events in early life have consistently been associated with health outcomes in later life. The ‘developmental origins’ theory first hypothesised that adverse conditions in-utero can lead to physiological adaptations in the developing foetus which have long lasting influences on health. This concept has been extended to early childhood and adolescence, whereby exposures during critical periods of development can impact health throughout the life course of an individual. In particular, a secular trend for a decreasing age of puberty onset has been linked to the global increases in prevalence of cardio-metabolic diseases and cancer. It has been suggested that childhood obesity and lifetime sex hormone exposure may act as key mediating factors in this relationship. As the prevalence of obesity continues to rise globally and consequent comorbidities place an increasing burden on healthcare systems, understanding the mechanisms that link early life events to later life health have become of increasing importance. While environmental exposures are often cited as being highly influential on growth and development, the role of genetics has become gradually more apparent in recent years. This has been aided by the availability of increasingly large data resources. Genetic studies have shown that many developmental traits are highly heritable and share genetic determinants with metabolic and reproductive health outcomes. In this thesis I use data from large-scale, population-based resources to further elucidate the role of genetic and epigenetic factors in explaining observed associations between developmental traits and later life metabolic and reproductive health. I begin by examining the genetic aetiology of puberty timing in men, a key stage of sexual development which is understudied compared to women. I identify 29 novel genes involved in the control of puberty timing, implicating new biological pathways and demonstrate genetic correlations between earlier age of puberty…
abstract: Events in early life have consistently been associated with health outcomes in later life. The ‘developmental origins’ theory first hypothesised that adverse conditions in-utero can lead to physiological adaptations in the developing foetus which have long lasting influences on health. This concept has been extended to early childhood and adolescence, whereby exposures during critical periods of development can impact health throughout the life course of an individual. In particular, a secular trend for a decreasing age of puberty onset has been linked to the global increases in prevalence of cardio-metabolic diseases and cancer. It has been suggested that childhood obesity and lifetime sex hormone exposure may act as key mediating factors in this relationship. As the prevalence of obesity continues to rise globally and consequent comorbidities place an increasing burden on healthcare systems, understanding the mechanisms that link early life events to later life health have become of increasing importance. While environmental exposures are often cited as being highly influential on growth and development, the role of genetics has become gradually more apparent in recent years. This has been aided by the availability of increasingly large data resources. Genetic studies have shown that many developmental traits are highly heritable and share genetic determinants with metabolic and reproductive health outcomes. In this thesis I use data from large-scale, population-based resources to further elucidate the role of genetic and epigenetic factors in explaining observed associations between developmental traits and later life metabolic and reproductive health. I begin by examining the genetic aetiology of puberty timing in men, a key stage of sexual development which is understudied compared to women. I identify 29 novel genes involved in the control of puberty timing, implicating new biological pathways and demonstrate genetic correlations between earlier age of puberty…
author: Hollis, Benjamin
language: eng
keywords: Genetics, Epidemiology, Growth, Development, Puberty
license: https://www.repository.cam.ac.uk/bitstreams/a805b5ec-90c6-4477-9a10-5a50c6ff1464/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2019-12-19
date modified: 2026-07-22T22:23:54Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.62304