Unraveling the causality between chronic obstructive pulmonary disease and its common comorbidities using bidirectional Mendelian randomization

Abstract

Abstract Background Chronic obstructive pulmonary disease (COPD) frequently coexists with various diseases, yet the causal relationship between COPD and these comorbidities remains ambiguous. As a result, the aim of our study is to elucidate the potential causality between COPD and its common comorbidities. Methods We employed the Mendelian randomization (MR) method to analyze single nucleotide polymorphism (SNP) data of common comorbidities with COPD from FinnGen and Integrative Epidemiology Unit (IEU) databases. Causality was primarily assessed using the inverse variance weighting (IVW) method. Multivariable Mendelian randomization (MVMR) analysis was also conducted to eliminate the interference of smoking-related phenotypes. Sensitivity analysis was conducted to ensure the reliability of our findings. Results Preliminary univariable MR revealed an increased risk of lung squamous cell carcinoma (LUSC) (IVW: OR = 1.757, 95% CI = 1.162–2.657, P = 0.008), chronic kidney disease (CKD) (IVW: OR = 1.193, 95% CI = 1.072–1.326, P < 0.001), chronic periodontitis (IVW: OR = 1.213, 95% CI = 1.038–1.417, P = 0.012), and heart failure (HF) (IVW: OR = 1.127, 95% CI = 1.043–1.218, P = 0.002). Additionally, the reverse MR analysis indicated that genetic susceptibility to HF (IVW: OR = 1.272, 95% CI = 1.084–1.493, P = 0.003), obesity (IVW: OR = 1.128, 95% CI = 1.056–1.205, P < 0.001), depression (IVW: OR = 1.491, 95% CI = 1.257–1.770, P < 0.001), and sleep apnea syndrome (IVW: OR = 1.209, 95% CI = 1.087–1.345, P < 0.001) could raise the risk of COPD. The MVMR analysis showed no causal effect of COPD on susceptibility to chronic periodontitis after adjusting for smoking. Conclusions Our study identified that COPD may elevate the risk of LUSC, HF, and CKD. Additionally, our analysis revealed that HF, sleep apnea symptoms, depression, and obesity might also increase the susceptibility to COPD. These findings revealed a potential causal relationship between COPD and several prevalent comorbidities, which may provide new insights for disease early prediction and prevention.