Assessing causality between chronic obstructive pulmonary disease with depression: A bidirectional Mendelian randomization study

Purpose: Our investigation utilized a two-sample Mendelian randomization approach to explore the ambiguous bidirectional relationship between Chronic Obstructive Pulmonary Disease (COPD) and depression, furthering insights from existing observational studies. Methods: In this study, we conducted a bidirectional Mendelian randomization using genome-wide association studies (GWAS) datasets. We initially analyzed depression data from the Psychiatric Genomics Consortium and the UK Biobank (n = 500,199), alongside COPD data from the FinnGen Consortium (n = 329,552). The second phase involved comparing depression data from FinnGen (n = 372,472) with COPD data from the UK Biobank (n = 361,194). Our Mendelian analysis employs various methods to guarantee a comprehensive and rigorous investigation. Results: In the initial analytic phase utilizing the inverse variance weighted (IVW) method, COPD does not significantly contribute to the incidence of depression (IVW odds ratio (OR) = 0.989, 95 % confidence interval (CI) = 0.895 to 1.092, P = 0.824). Conversely, the data suggested a statistically significant association where depression may precipitate the development of COPD, with a notable increase in risk (IVW OR = 1.421, 95 % CI = 1.149 to 1.756, P = 0.001). Subsequent validation through a second-step analysis reinforced the hypothesis that depression elevates the likelihood of COPD onset (IVW OR =1.002, 95 % CI =1.0003 to 1.0046, P = 0.028). Conclusion: Our study, utilizing Mendelian randomization analysis, determined that COPD does not escalate the risk of depression. Conversely, our analysis suggests that depression may elevate the risk of developing COPD. This insight underscores the importance of enhancing prevention, screening, and treatment strategies for COPD in individuals with depression.