Evaluation of bidirectional relationships between risk preference and mood disorders: A 2-sample Mendelian randomization study

Risk preference is often defined as the tendency to engage in risky activities. Increasing evidence shows that risk preference is associated with mood disorders. However, the causality and direction of this association are not clear. Genome-wide association study summary data of risk preference in 939,908 participants from UK Biobank and 23andMe were used to identify general risk preference. Data for 413,466 individuals taken from The Psychiatric Genomics Consortium were used to identify bipolar disorder (BP). Data for 807,553 individuals taken from The Psychiatric Genomics Consortium were used to identify major depressive disorder (MDD). The weighted median, inverse-variance weighting, and Mendelian randomization-Egger methods were used for the Mendelian randomization analysis to estimate a causal effect and detect directional pleiotropy. GWAS summary data were obtained from three combined samples, containing 939,908, 413,466 and 807,553 individuals of European ancestry. Mendelian randomization evidence suggested that risk preference increased the onset of BP, and BP also increased risk preference (P < 0.001). In contrast, there were no reliable results to describe the relationship of risk preference with MDD (P > 0.05). Furthermore, there was no significant relationship between MDD and risk preference. Using large-scale GWAS data, robust evidence supports a mutual relationship between risk preference and BP, but no relationship between risk preference and MDD was observed. This study indicates a potential marker for the early identification of MDD and BP. Additionally, it shows that reducing risk preferences for patients with BP may be a valuable intervention for treating BP.