Project 174136

Recent studies have clearly established a relationship between sub-optimal intrauterine and post-natal development, and later life predisposition to adult disease, including type II diabetes, hypertension, heart disease, stroke and other neurologic disorders - a relationship termed "developmental origins of health and disease" (DOHaD). While adverse pre- and post- natal development increases the risk of DOHaD it does not determine that an individual will acquire these disorders suggesting that interactions between an individual's genotype and the environment may contribute to the eventual outcome. Increasing evidence suggests that premature activation of the fetal hypothalamic-pituitary-adrenal (HPA) axis is a central component linking adverse pre and/or post-natal environmental exposures to later poor health outcomes. We propose to integrate population and murine developmental genetics approaches to investigate gene-environment interactions underlying DOHaD. Individually these approaches will provide important information regarding the pathogenesis of DOHaD; however, integrating these approaches capitalizes on their unique strengths and will enhance our progress towards future intervention strategies aimed at reducing the burden of these disorders.