Comparison of the multivariate genetic architecture of eight major psychiatric disorders across sex.

Differences in the patterning of genetic sharing between groups of individuals may arise from biological pathways, social mechanisms, phenotyping and ascertainment. We expand genomic structural equation modeling to allow for testing genomic structural invariance (GSI), that is, the formal comparison of multivariate genetic architecture across groups. We apply GSI to compare the autosomal multivariate genetic architecture of eight psychiatric disorders spanning three factors (psychotic, neurodevelopmental and internalizing) between cisgender males and females.

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.

Genomic Taxometric Analysis of Negative Emotionality and Major Depressive Disorder Highlights a Gradient of Genetic Differentiation across the Severity Spectrum.

A core question in both human genetics and medicine is whether clinical disorders represent extreme manifestations of continuous traits or categorically distinct entities with unique genetic etiologies. To address this question, we introduce data (GTACCC), a novel method for systematically evaluating continuity and differentiation of traits across the severity spectrum. GTACCC's key innovation lies in binarizing continuous data at multiple severity thresholds, enabling the estimation of genetic continuity and differentiation within the trait and in its relation to other traits via multivariate models.

Assessment and ascertainment in psychiatric molecular genetics: challenges and opportunities for cross-disorder research.

Psychiatric disorders are highly comorbid, heritable, and genetically correlated [1-4]. The primary objective of cross-disorder psychiatric genetics research is to identify and characterize both the shared genetic factors that contribute to convergent disease etiologies and the unique genetic factors that distinguish between disorders [4, 5]. This information can illuminate the biological mechanisms underlying comorbid presentations of psychopathology, improve nosology and prediction of illness risk and trajectories, and aid the development of more effective and targeted interventions.