Deciphering causality between social/physical activity and suicide attempt: evidence from Mendelian randomization.

Background: Previous research has indicated a link between social or physical activity and suicide attempt (SA), yet the causal relationship remains unclear, and the role of psychiatric disorders has not been elucidated.

Method: In this study, we used genetic variants of social or physical activity to examine the causal associations with SA based on iPSYCH database, and then replicate the results using FinnGen database.

Results: We found that sports clubs or gyms, walking for pleasure, light DIY and other exercises (e.g. bowling, swimming, cycling, and keep fit) may be protective factors for SA, while leisure/social inactivity may be risk factors. After FDR correction of P value, it was revealed that the OR [95%CI] of SA decreased per SD increase in walking for pleasure (0.23[0.07-0.73]), light DIY (0.21[0.07-0.59]), and other exercise (0.22[0.09-0.58]). Within the replication phase, genetic prediction analyses revealed that walking for pleasure, light DIY, and other exercises were associated with reduced susceptibility to SA (P_FDR < 0.05). Given the high comorbidity between psychiatric disorders and SA, we employed two-step MR and multivariate MR (MVMR) to evaluate the proportions the effect of the mediator. We found that Attention Deficit Hyperactivity Disorder (ADHD) explained 24.48% of the total effect of light DIY on SA, 33.52% of the total effect of other exercises.

Conclusion: Our research findings highlight the protective effect of social/physical activity in SA, and elucidated that increasing light DIY and other exercise can be used as a prevention strategy of SA, particularly for individuals who have ADHD.