Developmental origins of health and disease: The role of gene-environment interactions

The 'Developmental Origins of Health and Disease' (DOHaD) hypothesis states that adverse environments in early life can have lifelong and irreversible impacts, affecting individuals’ health and well-being in older age. Barker and colleagues show that the infant mortality rate in early life is a significant predictor of later life cardiovascular disease. This paper starts by replicating these findings. For this, we digitize data on infant mortality rates across approximately 1500 Local Government Districts in England and Wales over 40 years, and merge this with the UK Biobank; a major resource that follows the health and well-being of approximately 500,000 individuals in the UK aged 40-69 between 2006-2010. We then test whether an individual’s genetic predisposition, as measured by their polygenic score, mediates the effects of such adverse early life conditions. For example, we test whether a higher polygenic score for educational attainment can protect individuals against such adverse early life conditions.