Mental illness and pulmonary tuberculosis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies have confirmed that mental illness and pulmonary tuberculosis are closely related and increase each other's incidence; however, whether there is a causal genetic association between the two diseases remains unknown. We attempted to answer this question using bidirectional two-sample Mendelian randomization (MR) in a large cohort study.

Method: We performed a bidirectional MR analysis between mental illness (major depressive, anxiety disorder, bipolar disorder, and schizophrenia) and pulmonary tuberculosis using summary statistics from genome-wide association studies in European individuals. The inverse-variance weighted method was used as the primary analytical method to assess causality. In addition, other additional MR methods (weighted median, MR-Egger, and weighted mode) were used to supplement the inverse-variance weighted results. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability.

Result: We identified no causal genetic association between mental illness and pulmonary tuberculosis after applying the inverse variance weighted method (major depressive: odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.59-1.71, = 0.98; anxiety disorder: OR = 1.72, 95% CI = 0.05-67.67, = 0.76; bipolar disorder OR = 0.89, 95% CI = 0.66-1.22, = 0.48; and schizophrenia: OR = 1.05, 95% CI = 0.91-1.20, = 0.51). Similarly, pulmonary tuberculosis was not caustically associated with mental illness (major depressive: OR = 1.01, 95% CI = 1.00-1.02, = 0.17; anxiety disorder: OR = 1.00, 95% CI = 0.99-1.01, = 0.06; bipolar disorder: OR = 1.02, 95% CI = 0.98-1.07, = 0.38; and schizophrenia: OR = 1.01, 95% CI = 0.97-1.05, = 0.66).

Conclusion: Our research does not support a bidirectional causal association between the aforementioned mental illnesses and pulmonary tuberculosis.