Multivariate GWAS of psychiatric disorders and their cardinal symptoms reveal two dimensions of cross-cutting genetic liabilities

• DOI: 10.1016/j.xgen.2022.100140
• Publication Date: 2022-06-08T17:13:35Z
• Authors: Travis T. Mallard; Richard Karlsson ...; Andrew D. Grotzinger; Sandra Sanchez-Roige; Jakob Seidlitz; Aysu Okbay; Ronald de Vlaming; S. Fleur W. Meddens; Abraham A. Palmer; Lea K. Davis; Elliot M. Tucker-...; Kenneth S. Kendler; Matthew C. Keller; Philipp D. Koelli...; K. Paige Harden
• Keywords: Nosology; Genome-wide Association Study; Association (psychology)

Understanding which biological pathways are specific versus general across diagnostic categories and levels of symptom severity is critical to improving nosology treatment psychopathology. Here, we combine transdiagnostic dimensional approaches genetic discovery for the first time, conducting a novel multivariate genome-wide association study eight psychiatric symptoms disorders broadly related mood disturbance psychosis. We identify two liabilities that distinguish between common forms psychopathology rarer serious mental illness. Biological annotation revealed divergent architectures differentially implicated prenatal neurodevelopment neuronal function regulation. These findings inform models psychopathology, as they suggest psychotic present in illness may reflect difference kind rather than merely degree.