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. 2025 Jul 11;104(28):e43306.
doi: 10.1097/MD.0000000000043306.

Association between Streptococcus and chronic obstructive pulmonary disease: A two-sample Mendelian randomization study

Ziqi Ding  1 , Xinru Xiao, Na Li, Chuang Sun, Yujia Shi
Affiliations

Association between Streptococcus and chronic obstructive pulmonary disease: A two-sample Mendelian randomization study

Ziqi Ding et al. Medicine (Baltimore). .

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.

Keywords: Mendelian randomization; chronic obstructive pulmonary disease.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Overview of MR analyses process and major assumptions. MR = Mendelian randomization.
Figure 2.
Figure 2.
Forrest plot for summary causal effects of gut microbiota on COPD risk. COPD = chronic obstructive pulmonary disease.
Figure 3.
Figure 3.
Scatter plots of the MR analyses for the association of gut microbiota and the risk of COPD. COPD = chronic obstructive pulmonary disease.
See this image and copyright information in PMC

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