Arun Durvasula: Understanding gene-environment interactions in complex traits and disease

The role of gene-environment (GxE) interaction in disease and complex trait architectures is widely hypothesized, but currently unknown. In the first part of the talk, I will discuss new approaches to measuring the contribution of polygenic GxE to complex traits using three complimentary statistical approaches based on genetic correlation, SNP-heritability differences, and polygenic risk score (PRS) by E regression. In the second part of the talk, I will discuss gene-by-age interactions and how genetic risk varies across age for several common diseases including type 2 diabetes, hypertension, and hypercholesterolemia. I will discuss interpretations of this variation and the impact on polygenic risk prediction accuracy. In the third part of the talk, I will discuss leveraging proteomic data to putative gene-environment interactions by identifying non-linear mediators of an outcome that are driven by genetic and environmental variation.