Missing genetic links between general factors of brain resting-state functional magnetic resonance imaging, cognition and psychopathology

Abstract

General factors capturing the shared genetics in psychiatric (genomic p-factor) and cognitive traits (genomic g-factor), and more recently in resting-state functional magnetic resonance imaging-derived brain networks, have contributed to our increased understanding of the etiologies in their respective domains. Yet it remains unclear whether general factors can capture the three-way genetic overlap of psychopathology, cognition and brain function. Here we tested for the presence of this genetic overlap via genetic correlation analyses using summary statistics of genome-wide association studies of the p-factor (N = 162,151 cases and 276,846 controls), the g-factor (N = 269,867), and the two genomic factors estimated from the amplitude in resting-state functional magnetic resonance imaging-derived brain networks (N = 31,688). Unlike hypothesized, only the genetic correlation between the p-factor and the g-factor was significant. We conclude that specific functional brain network constructs may have more potential than their derived general dimensions to capture relevant genetic variation for cognition and psychopathology.