Leveraging large-scale genetic and epigenetic data to infer genomic responses to environmental pressures in humans

Humans have shown remarkable resilience to a variety of environmental pressures, such as pathogens and climate change. Sometimes patterns we inherit in our DNA sequence have enabled our adaptation, as genes encoding mechanisms vital to survival have propagated through time, with many such conserved genetic regions linked to disease. Parallel to genetics, our so-called methylome can activate or deactivate specific genes in response to environmental factors, even within our lifetime. This project will identify (1) genetic sequence variants that have facilitated past adaptations and (2) genetic regions through which the environment we are exposed to in our early embryo can alter our methylome and hence influence lifelong health. We will do so by developing innovative mathematical models that capture shared signatures of these effects across data from thousands of world-wide people sampled through hundreds of studies. In doing so, this work will illuminate key genetic pathways affecting health today.