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

F. Wendt,G. Pathak,T. Lencz,J. Krystal,J. Gelernter,R. Polimanti

Published 2020 in Nature Human Behaviour

ABSTRACT

Socioeconomic status (SES) and education (EDU) are phenotypically associated with psychiatric disorders and behaviours. It remains unclear how these associations influence genetic risk for psychopathology, psychosocial factors and EDU and/or SES (EDU/SES) individually. Using information from >1 million individuals, we conditioned the genetic risk for psychiatric disorders, personality traits, brain imaging phenotypes and externalizing behaviours with genome-wide data for EDU/SES. Accounting for EDU/SES significantly affected the observed heritability of psychiatric traits, ranging from 2.44% h2 decrease for bipolar disorder to 14.2% h2 decrease for Tourette syndrome. Neuroticism h2 significantly increased by 20.23% after conditioning with SES. After EDU/SES conditioning, neuronal cell types were identified for risky behaviour (excitatory), major depression (inhibitory), schizophrenia (excitatory and γ-aminobutyric acid (GABA) mediated) 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. Accounting for the genetic effects of education and socioeconomic status, psychopathology and psychosocial factors revealed trait-specific genetic architecture, associated biological inference and correlative and putatively causal relationships.

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