Joint effects of childhood adversity and genetic risk for psychosis on psychopathology in the UK Biobank

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Abstract Background The individual effects of genetic factors and adverse childhood experiences (ACEs) on risk of psychosis, including schizophrenia (SCZ) and bipolar disorder (BIP), have been widely acknowledged, but their interaction effects on individual psychopathological symptoms remain unclear. Methods Based on data from 163,704 individuals in the UK Biobank, we investigated the joint effects of polygenic risk scores (PRSs) of SCZ and BIP and ACEs on psychopathology. ACEs status and 55 psychopathological symptoms from seven domains were measured retrospectively using an online mental health questionnaire in 2016. Recent genome-wide association studies for SCZ and BIP were combined with genotype data to generate PRSs. Logistic regression analyses were then conducted to explore univariate and joint main effects of PRSs and ACEs on psychopathological symptoms, as well as their additive and multiplicative interaction effects. Results The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERI BIP-ACEs = 0.20–0.25), anxiety (RERI SCZ-ACEs = 0.20; RERI BIP-ACEs = 0.22–0.26), help-seeking (RERI SCZ-ACEs = 0.24; RERI BIP-ACEs = 0.23), and cognition domains (RERI SCZ-ACEs = −0.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (beta SCZ-ACEs = −0.543; beta BIP-ACEs = −0.181), mania (beta BIP-ACEs = −0.195), self-harm or suicide (beta SCZ-ACEs = −0.118), and cognitive domains (beta SCZ-ACEs = −0.204 to −0.157). Conclusions The interplay mechanisms for genetic liability to SCZ and BIP and ACEs vary across symptom domains. This study reveals heterogeneity in gene–ACEs interaction mechanisms underlying psychosis and may provide personalized guidance for psychological care after ACEs.

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