Associations Between Sleep Traits and Risk of Suicide Attempt: Insight from A Two-Sample Mendelian Randomization Analysis

Background Sleep-related traits were associated with the risk of suicide attempt (SA) in observational epidemiological studies. However, little is known regarding the causal associations between them.Objectives To evaluate the potential causal associations between sleep traits and risk of SA using a two-sample Mendelian randomization (MR) design.Methods Genetic instruments robustly associated with sleep traits were selected from corresponding genome-wide association studies. Summary statistics for SA were obtained from the FinnGen consortium and the Psychiatric Genomics Consortium (PGC). Inverse variance-weighted method was employed as the primary method, and several other MR methods under different assumptions were performed as sensitivity analyses. Additionally, multivariable MR analyses were further conducted to assess the independent effects of sleep traits on SA after adjusting for educational attainment, smoking initiation, and alcohol consumption. Results from two databases were combined using random-effects meta-analysis.Results In the meta-analysis of two data sources, genetic liability to insomnia was significantly associated with an increased risk of SA (odds ratio [OR] = 1.29, 95% confidence interval [CI]: 1.23–1.35, p < 0.001). The association remained stable in multivariable MR analysis with adjustment for educational attainment (OR = 1.25, 95% CI: 1.19–1.32, p < 0.001), smoking initiation (OR = 1.25, 95% CI: 1.19–1.32, p < 0.001), and alcohol consumption (OR = 1.28, 95% CI: 1.22–1.34, p < 0.001). However, there was no significant evidence supporting the causal associations of chronotype, sleep duration, short sleep duration, and long sleep duration with risk of SA.Conclusions The present MR study provides the supportive evidence for insomnia being a causal risk factor for SA.