Using genetics to understand how modifiable lifestyle changes may prevent disease in later life: A life course approach

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Understanding the manner in which modifiable factors (including lifestyle) during childhood and adolescence influence our risk of disease is challenging. For instance, individuals who are obese in early life have elevated risk of cardiovascular disease. However, as these individuals tend to remain obese into later life, it is unclear how much of this conferred risk can be reversed by making lifestyle changes. Furthermore, complex disease is typically determined by multiple risk factors, which may or may not act independently of one and other. This PhD will use large datasets to develop a putative causal map of how multiple lifestyle factors influence disease risk. There will be an emphasis on early life exposures, as results suggesting that conferred risk during childhood can be reversed will have an important translatable message that can impact social policy. Conversely, it is imperative to better understand which early life risk factors have an immutable influence on disease susceptibility which cannot be mitigated through lifestyle modifications. The principles of a technique in epidemiology known as Mendelian randomization (MR) will be applied. This approach uses genetics to disentangle causal relationships, which is particularly powerful given that our genes are inherited randomly at birth. As such they are robust to factors such as confounding and reverse causation which hinder observational analyses.