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

Area of Science:

• Psychiatric Genomics
• Behavioral Genetics
• Neuroscience

Background:

• Risk preference, the tendency towards risky activities, is increasingly linked to mood disorders.
• The causal relationship and directionality between risk preference and mood disorders remain unclear.

Purpose of the Study:

• To investigate the causal relationship between general risk preference and bipolar disorder (BP) and major depressive disorder (MDD).
• To utilize large-scale genome-wide association study (GWAS) data and Mendelian randomization (MR) analysis for robust causal inference.

Main Methods:

• Employed MR analysis using summary statistics from large GWAS datasets (UK Biobank, 23andMe, Psychiatric Genomics Consortium).
• Utilized weighted median, inverse-variance weighting, and MR-Egger methods to assess causality and detect pleiotropy.
• Analyzed data from 939,908 individuals for risk preference, 413,466 for BP, and 807,553 for MDD.

Main Results:

• MR analysis revealed a significant bidirectional causal relationship between risk preference and bipolar disorder (BP) (P < 0.001).
• No reliable causal association was observed between risk preference and major depressive disorder (MDD) (P > 0.05).

Conclusions:

• Robust evidence supports a mutual relationship between risk preference and BP, but not MDD.
• Findings suggest risk preference may serve as a potential marker for early identification of BP.
• Reducing risk preference in BP patients could be a valuable therapeutic intervention.