Interplay between polygenic risk for mood disorders and stressful life events in bipolar disorder

Although genetic and environmental factors are involved in the aetiology of bipolar disorder [BD], studies focused on their interplay are lacking. The current investigation examines interactions and correlations between polygenic risk scores [PRS] for BD and major depressive disorder [MDD] with stressful life events [SLEs] in liability for BD.

This study used data from 1715 participants (862 bipolar cases and 853 controls) taken from UK and Canadian samples. The List of Threatening Experiences Questionnaire recorded SLEs that occurred 6 months before interview for controls and 6 months prior to the first (Canadian sample) and worst (UK sample) depressive and manic episodes for bipolar cases. PRS-BD and PRS-MDD were calculated from the Psychiatric Genomics Consortium.

For the worst depressive episode, the PRS-MDD was significantly correlated with total number of SLEs (β = 0.13, 95 % CI:0.04-0.22, p = 0.003) and dependent SLEs (β = 0.09, 95 % CI:0.02-0.16, p = 0.007). After correction for multiple testing nominally significant correlations were detected for PRS-BD with total number of SLEs (β = 0.11, 95 % CI:0.02-0.20, p = 0.015) and dependent SLEs (β = 0.08, 95 % CI:0.01-0.15, p = 0.019). Among bipolar cases, these associations were slightly stronger but were only of nominal significance for total number of SLEs (PRS-MDD: β = 0.19, 95 % CI:0.04-0.35, p = 0.015; PRS-BD: β = 0.16, 95 % CI:0.01-0.32, p = 0.042) and dependent SLEs (PRS-MDD: β = 0.14, 95 % CI:0.03-0.26, p = 0.015; PRS-BD: β = 0.12, 95 % CI:0.004-0.24, p = 0.043). No other significant gene-environment correlations or interactions were found.

Use of a larger sample size would be beneficial.

The relationship between SLEs and genetic risk for mood disorders may be best explained through correlations rather than interactions.