Crystallized and fluid cognitive abilities have different genetic associations with neuropsychiatric disorders

Cognitive function is associated with risk for multiple neuropsychiatric disorders. Previous research on the genetic relations between cognition and psychopathology has largely treated cognitive function as unitary, in part due to a lack of well-powered genome-wide association studies (GWAS) on specific domains, particularly crystallized knowledge (Gc). Important domains within the hierarchy of cognitive function, especially Gc, have been underexplored regarding their associations with psychiatric disorders. Here, we parse the genetics of cognitive test performance into components representing reaction time, fluid reasoning, and crystallized knowledge. This multivariate approach that allows us to report results from a GWAS meta-analysis of crystallized knowledge (N ~ 438,000). We then test how multiple neuropsychiatric disorders with established links to cognitive function (Schizophrenia, Bipolar Disorder, Autism Spectrum Disorder, Attention Deficit Hyperactivity Disorder, and Alzheimer's Disease) are genetically related to these three cognitive domains, and to a noncognitive factor associated with educational attainment (NonCog). We document specific and heterogenous patterns of genetic associations between each neuropsychiatric disorder and the different domains of cognitive function and the noncognitive factor. Previous reports of genetic sharing between neuropsychiatric disorders and GWAS of aggregate cognitive function or educational attainment have failed identify these substantial differences in which cognitive functions drive these relations for which disorders.