Panos Roussos, MD, MS, PhD

Professor of Psychiatry and Genetics and Genomic Sciences, Director of the Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai

Decoding Brain Disease Heterogeneity through Population-Scale Multimodal Genomics

Brain disorders arise from genetic and environmental perturbations that act within specific cell types and regulatory programs, yet connecting these molecular effects to disease heterogeneity and clinically meaningful outcomes remains challenging. I will present population-scale, multimodal approaches that integrate single-nucleus transcriptomic and epigenomic data with human genetics, neuropathology, and clinical phenotypes across thousands of donors. Drawing on the PsychAD and GENESIS programs, I will describe computational frameworks for harmonizing large single-cell datasets, mapping genetic risk to disease-relevant cell types and regulatory networks, and developing genetically informed models applicable to large clinical cohorts. These studies illustrate how multimodal genomics and AI can move beyond descriptive cellular atlases toward models of cellular vulnerability and resilience, ancestry-aware molecular prediction, patient stratification, and therapeutic prioritization.