Increased risk of the onset and exacerbation of COPD in metabolic syndrome patients: A 2-sample Mendelian randomization study.

This study aimed to assess the genetic associations of metabolic syndrome (MetS) and its components with the onset and exacerbation of chronic obstructive pulmonary disease (COPD), including respiratory failure and pneumonia. Summary statistics were sourced from publicly available genome-wide association studies. Genetic instruments were selected at genome-wide significance and linkage disequilibrium clumped via PLINK software. Instrument strength was confirmed using F-statistics. Mendelian randomization (MR) analyses were performed using inverse-variance weighted, maximum likelihood, MR-Egger, and median-based approaches. Multivariable MR was performed to determine the independent effects of MetS and waist circumference (WC). Sensitivity analysis was performed to validate the robustness of the results. Statistical power was evaluated a priori using the mRnd. We controlled for multiple comparisons using the Benjamini-Hochberg false discovery rate procedure and reported the q-values. Using the inverse variance weighted method, MetS was associated with an increased risk of COPD onset (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 1.14-1.40), respiratory insufficiency (OR = 1.66, 95% CI: 1.34-2.06), and pneumonia (OR = 1.13, 95% CI: 1.08-1.19). Among components, WC exhibited the strongest associations with COPD (OR = 1.69, 95% CI: 1.54-1.84), respiratory insufficiency (OR = 2.27, 95% CI: 1.89-2.72), and pneumonia (OR = 1.20, 95% CI: 1.16-1.25). Hypertension showed a nominal association with pneumonia (OR = 1.10, 95% CI: 1.00-1.20, P = .040, q = 0.103), which did not remain significant after false discovery rate correction. The other components showed no causal associations with COPD. Our study provides genetic evidence consistent with the causal contribution of MetS to COPD onset and exacerbation, with central adiposity (WC) emerging as the dominant driver. This finding supports closer respiratory risk assessment and prevention efforts among patients with MetS. Patients with comorbid COPD and MetS require personalized multidisciplinary strategies to prevent COPD exacerbation and slow progression.