Multiple psychiatric polygenic risk scores predict associations between childhood adversity and bipolar disorder

Abstract

Background: It remains unclear how adverse childhood experiences (ACE) and increased genetic risk for bipolar disorder (BD) interact to influence BD symptom outcomes. Here we calculated multiple psychiatric polygenic risk scores (PRS) and used the measures of ACE to understand these gene-environment interactions.

Method: 885 BD subjects were included for analyses. BD, ADHD, MDD and SCZ PRSs were calculated using the PRS-CS-auto method. ACEs were evaluated using the Children Life Event Questionnaire (CLEQ). Participants were divided into groups based on the presence of ACE and the total number of ACEs. The associations between total ACE number, PRSs and their interactions were evaluated using multiple linear and logistic regressions. Secondary analyses were performed to evaluate the influence of ACE and PRS on sub-phenotypes of BD.

Results: The number of ACEs increased with the ADHD PRS. BD participants who had ACEs showed an earlier age of BD onset and higher odds of having rapid cycling. Increased BD PRS was associated with increased odds of developing psychotic symptoms. Higher ADHD PRS was associated with increased odds of having rapid cycling. No prediction effect was observed from MDD and SCZ PRS. And, we found no significant interaction between ACE numbers and any of the PRSs in predicting any selected BD sub-phenotypes.

Limitations: The study was limited by sample size, ACE definition, and cross-sectional data collection method.

Conclusions: The findings consolidate the importance of considering multiple psychiatric PRSs in predicting symptom outcomes among BD patients.

Keywords: Adverse childhood experiences; Attention-deficit/hyperactivity disorder; Bipolar disorder; Major depressive disorder; Polygenic risk score; Schizophrenia.