BIDS Grand Rounds

Title: Single-cell Polygenic Risk Scores

Abstract: Polygenic risk scores (PRSs) predict an individual’s genetic risk for complex diseases, yet their utility in elucidating disease biology remains limited. In this talk, I will introduce scPRS, a graph neural network-based framework that computes single-cell-resolved PRSs by integrating reference single-cell chromatin accessibility profiles. scPRS outperforms traditional PRS approaches in genetic risk prediction, as demonstrated across multiple diseases including type 2 diabetes, hypertrophic cardiomyopathy, Alzheimer disease and severe COVID-19. Beyond risk prediction, scPRS prioritizes disease-critical cells and, when combined with a layered multiomic analysis, links risk variants to gene regulation in a cell-type-specific manner. Applied to these diseases, scPRS fine-maps causal cell types and cell-type-specific variants and genes, demonstrating its ability to bridge genetic risk with cell-specific biology. scPRS provides a unified framework for genetic risk prediction and mechanistic dissection of complex diseases, laying a methodological foundation for single-cell genetics.

CME accredited seminar. Information for claiming credit will be provided at the start of the session.