Investigating the causal effects of smoking, sleep, and BMI on major depressive disorder and bipolar disorder: a univariable and multivariable two-sample Mendelian randomization study.

Background: Mental disorders, characterized as products of biopsychosocial interactions, have emerged as a leading contributor to the worldwide rise in overall morbidity and disability rates. Life's essentials can affect nearly every aspect of our lives, from physical to mental health. In this study, we try to identify the associations between life's essentials and mental disorders. Method: Three assumptions of Mendelian randomization (MR) were applied to obtain the genetic instruments associated with smoking, sleep, and body mass index (BMI) in genome-wide association studies. Then, we conducted univariable MR (UVMR) and multivariable MR (MVMR) two-sample analyses to estimate the causal effects of these life's essentials on two mental disorders namely, major depressive disorder (MDD) and bipolar disorder (BD). Additionally, multiple sensitivity analyses were performed to evaluate the reliability and stability of the study results. Results: In the MR analysis of the association of smoking, sleep, and BMI with MDD, we obtained 78, 39, and 302 genetic instruments, respectively. Smoking [odds ratio (OR), 1.03; 95% confidence interval (CI), 1.01-1.06; Conclusion: The study results provide strong evidence that smoking, sleep, and BMI are causally related to MDD and BD, which need further research to clarify the underlying mechanism.