LAUSR

BACKGROUND The interactions and associations between insomnia, depressive symptoms, and subjective well-being are complex, thus it is hard to explore the effect and direction of causalities. This bidirectional Mendelian randomization (MR) study was to assess the causal associations of insomnia with depressive symptoms and subjective well-being. METHODS Summary statistics for insomnia, depressive symptoms, and subjective well-being were obtained from three large-scale genome-wide association studies (GWAS) of European ancestry. MR analyses were mainly conducted with the inverse-variance-weighted (IVW) method. The weighted-median method, MR-Egger method, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) test were adopted to test whether the estimates were robust. The adjusted MR analysis was performed to avoid the effect of potential pleiotropy. RESULTS There was evidence to support a causal association between genetically predicted insomnia and depressive symptoms (beta (β) = 0.086, 95% confidence interval (CI) = 0.068 to 0.104, P = 8.6E-21). Meanwhile, genetically predicted depressive symptoms was associated with a higher risk of insomnia (β = 0.543, 95% CI = 0.331 to 0.754, P = 4.8E-07). Genetically predicted insomnia was negatively associated with subjective well-being (β = -0.043, 95% CI = -0.063 to -0.024, P = 1.2E-05). There was evidence of reverse causality between insomnia and subjective well-being (β = -0.821, 95% CI = -1.012 to -0.630, P = 4.0E-17). CONCLUSIONS MR analysis indicates bidirectional causal associations of insomnia with depressive symptoms and subjective well-being. People should give serious attention to and attempt to resolve the problems of insomnia, depressive symptoms, and subjective well-being, whichever comes first.