Multivariate genome-wide analysis of education, socioeconomic status, and brain phenome

Socioeconomic status (SES) and education (EDU) are phenotypically associated with psychiatric disorders and behaviors. It remains unclear how these associations influence genetic risk for psychopathology, psychosocial factors, and EDU/SES individually. Using information from >1 million individuals, we conditioned the genetic risk for psychiatric disorders, personality traits, brain imaging phenotypes, and externalizing behaviors with genome-wide data for EDU/SES. Accounting for EDU/SES significantly affected the observed heritability of psychiatric traits ranging from 2.44% h(2) decrease for bipolar disorder to 14.2% h(2) decrease for Tourette syndrome. Neuroticism h(2) significantly increased by 20.23% after conditioning with SES. After EDU/SES conditioning, neuronal cell-types were identified for risky behavior (excitatory), major depression (inhibitory), schizophrenia (excitatory and GABAergic), and bipolar disorder (excitatory). Conditioning with EDU/SES also revealed unidirectional causality between brain morphology, psychopathology, and psychosocial factors. Our results indicate that genetic discoveries related to psychopathology and psychosocial factors may be limited by genetic overlap with EDU/SES.