Approved Research

Applying strategies for lifecourse epidemiology by combining genetics, the principles of Mendelian randomisation and longitudinal observational methods

Lay summary

Often diseases diagnosed in adulthood have physiological antecedents that begin in early life. Gaining a better understanding of how the timing of exposures at different stages in the lifecourse influence health outcomes is key to identifying when the effects of risk factors driving health inequalities may be reversed through lifestyle or environmental modifications. A lifecourse approach crucially investigates the contribution of early and later life exposures together, to identify risk and protective mechanisms across the lifespan. Separating the effects of risk factors at different stages of the lifecourse is challenging, particularly due to the influence of confounding factors; variables that influences both the exposure and outcome of interest, causing a spurious association. Mendelian randomisation (MR) exploits the random assortment of genetic variants, independent of other traits, to enable analyses that largely mitigate against distortions resulting from confounding and reverse causality, which afflict epidemiological observational research. However, whilst it has been shown that genetic associations may arise from the direct effects of the same inherited genetic variants at different stages of the lifecourse, there are only a handful of studies that have incorporate a lifecourse approach using genetics and applying the principles of MR.

This study sets out to assess disease risk in later life by employing instruments used to separate exposures at different stages in the lifecourse to elucidate modifiable pathways at critical time points. The more we understand about causal risk factors across the lifecourse, the more effective our interventions will be.