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Association between Streptococcus and chronic obstructive pulmonary disease: A two-sample Mendelian randomization
1Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China.
Abstract:
Streptococcus is one of the most common causative agents of acute exacerbations of chronic obstructive pulmonary disease (COPD). It may cause infection and inflammation in the lungs, leading to dyspnea and other symptoms. However, the causal connection between Streptococcus and COPD has not been elucidated. This study aimed to investigate the causal relationship between Streptococcus and the risk of COPD. Using a large-scale genome-wide association study database, a series of quality control steps were taken to select qualified single nucleotide polymorphisms that were strongly associated with exposure. Two-sample Mendelian randomization (MR) was used to evaluate the causal effect of Streptococcus on COPD, including inverse variance weighting, MR-Egger, weighted median, weighted mode, and simple mode. MR-Egger intercept tests, Cochran Q test, MR-PRESSO global test, and "leave-one-out" sensitivity analyzes were applied to assess horizontal pleiotropy, heterogeneity, and stability. Based on extensive genetic data obtained from genome-wide association studies involving 468,475 European participants, we included a total of 14 single nucleotide polymorphisms as instrumental variables. MR results confirmed an association between Streptococcus and a higher risk of COPD (odds ratio = 1.18, confidence interval = 1.01-1.38, P = 4.28 × 10-2). Analyses of heterogeneity (P > .05) and pleiotropy (P > .05) analysis confirmed the reliability of MR results. We verified the possibility of a causal link between Streptococcus and COPD, thereby highlighting the connection of the gut-lung axis.
Insights
This study investigated the link between Streptococcus bacteria and chronic obstructive pulmonary disease (COPD). Findings suggest Streptococcus may causally increase the risk of developing COPD, highlighting the gut-lung axis connection.
Area of Science:
- Genetics
- Microbiology
- Pulmonology
Background:
- Streptococcus is a common cause of acute exacerbations in chronic obstructive pulmonary disease (COPD).
- The direct causal link between Streptococcus and COPD development remains unclear.
- Understanding this relationship is crucial for managing COPD and its triggers.
Purpose of the Study:
- To investigate the potential causal relationship between Streptococcus and the risk of developing COPD.
- To leverage genetic data for a robust assessment of this association.
- To explore the gut-lung axis in the context of COPD pathogenesis.
Main Methods:
- Utilized a large-scale, two-sample Mendelian randomization (MR) study design.
- Employed genome-wide association study (GWAS) data from 468,475 European participants.
- Selected 14 single nucleotide polymorphisms (SNPs) as instrumental variables and applied various statistical methods (IVW, MR-Egger, etc.) for causal inference.
Main Results:
- Mendelian randomization analysis indicated a significant association between Streptococcus and an increased risk of COPD (OR=1.18, CI=1.01-1.38).
- Sensitivity analyses for heterogeneity and pleiotropy confirmed the reliability and stability of the findings.
- No significant heterogeneity (P>0.05) or pleiotropy (P>0.05) was detected, supporting the validity of the results.
Conclusions:
- This study provides evidence supporting a potential causal link between Streptococcus and an elevated risk of COPD.
- The findings underscore the importance of the gut-lung axis in the development of COPD.
- Further research into Streptococcus's role may inform novel therapeutic strategies for COPD prevention and management.
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