Jordan Smoller Seminar, March 11, 2026

In this seminar, Dr. Jordan Smoller presents an overview of cross-disorder genetics in psychiatry, highlighting the progress made in identifying genetic risk variants for psychiatric disorders. He discusses the challenges of psychiatric phenotyping, noting the limitations of DSM categories and the high comorbidity among disorders. The talk covers key methodological advances, including LD score regression and genomic structural equation modeling, which have enabled large-scale analyses of genetic overlap. Smoller presents findings from the Psychiatric Genomics Consortium, showing substantial genetic correlations between disorders like schizophrenia and bipolar disorder. He introduces the concept of latent genomic factors, such as the compulsive disorders factor and the mood-psychotic factor, which capture shared genetic architecture. The seminar also explores pleiotropic loci, like DCC and NRXN1, and their potential biological roles. Recent work with 14 disorders reveals a correlated factors model with five latent factors, and a p-factor capturing transdiagnostic vulnerability. Functional genomic analyses suggest that pleiotropic genes are involved in fundamental processes and are highly expressed in fetal brain. The talk concludes with implications for understanding psychiatric disorders and potential future directions.