DONNI SIGNED

Project "DONNI" data sheet

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 Partnership

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 Project objective

The “Developmental Origins of Health and Disease” (DOHaD) hypothesis states that insults in early life can have lifelong, irreversible impacts, affecting individuals’ health and well-being in older age. My proposed research builds on this in two main ways. First, I will use natural experiments to investigate the causal impact of early life circumstances on later life outcomes, focusing on novel (1) nutritional, (2) toxicological, (3) health and (4) economic environments in early life. Within these, I will consider insults (i) for which there is insufficient knowledge of their long-term impacts, (ii) which are relevant today, and (iii) importantly, which are modifiable. Second, I will go beyond the old “nature versus nurture” debate and investigate how individuals’ genes (‘nature’) interacts with the above early life environments (‘nurture’) in creating inequalities in health and well-being.

Whilst neither the estimation of causal effects within DOHaD, nor the estimation of the gene-environment (GxE) interplay is new, their combination is. Indeed, it is currently not known how the early life environment interacts with genetic predisposition to causally shape later life outcomes, as well as whether certain environments exacerbate or reduce health inequalities in the population. Combining advancements across disciplines, I will evaluate the long-term effects of short-term variations in early life conditions (objective 1), and I will directly test the hypothesis that gene-environment interactions causally shape later life outcomes (objective 2). I will digitize historical data on early life environmental exposures and merge these with large-scale individual-level data. As such, my proposal will investigate the extent to which genes interact with the environment, using natural experiments to identify interventions that can ameliorate inequalities in health and well-being (objective 3).