Dataset Information

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

ABSTRACT:

Background

A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.

Methods

The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen consortium. Summary-level dataset for COPD were obtained from the FinnGen consortium. The main analysis method for determining the causal link between gut microbiota and COPD was inverse variance weighted (IVW). Subsequently, pleiotropy and heterogeneity tests were performed to determine the reliability of the results.

Results

IVW method identified 9 bacterial taxa nominally associated with the risk of COPD. Class Actinobacteria (p = 0.020), genus Allisonella (p = 0.024), genus Coprococcus2 (p = 0.002) and genus Oscillospira (p = 0.018) were protective against COPD. In addition, order Desulfovibrionales (p = 0.011), family Desulfovibrionaceae (p = 0.039), family Peptococcaceae (p = 0.020), family Victivallaceae (p = 0.012) and genus Marvinbryantia (p = 0.017) were associated with a higher risk of COPD. No pleiotropy or heterogeneity were found.

Conclusion

According to the findings of this MR analysis, a causal relationship exists between certain gut microbiota and COPD. New insights into the mechanisms of COPD mediated by gut microbiota are provided.

SUBMITTER: Wei Y

PROVIDER: S-EPMC10315658 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

Wei Yi Y Lu Xuechao X Liu Chao C

Frontiers in microbiology 20230619

<h4>Background</h4>A growing number of studies implies a strong association between gut microbiota and chronic obstructive pulmonary disease (COPD). However, the causal impact between gut microbiota and COPD remains unclear. As a result, we used a two-sample Mendelian randomization (MR) method to investigate the connection between gut microbiota and COPD in this study.<h4>Methods</h4>The largest available genome-wide association study (GWAS) of gut microbiota was obtained from the MiBioGen conso ...[more]

PMID: 37405157

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Project description:BackgroundChronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD.MethodsCis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases.ResultsA total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1.ConclusionsOur findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.

Project description:BackgroundPrevious observational studies have reported an association between chronic obstructive pulmonary disease (COPD) and osteoporosis (OP). The aim of this study is to investigate the causal relationship between COPD and OP by two-sample Mendelian randomization (MR) analysis. The current status of cross-sectional research between COPD and OP in the past decade was explored through bibliometrics.MethodsSingle nucleotide polymorphisms (SNPs) that have been found to be strongly associated with COPD were used as instrumental variables (IVs) in MR Analysis. The primary outcome of the study was BMD measurement at five specific anatomical sites, namely the whole body, femoral neck, lumbar spine, forearm, and heel. These BMD measurements were derived primarily from a genome-wide association study (GWAS) and summary statistics from the International Genetic Factors Consortium for Osteoporosis (GEFOS). The main analysis method was inverse variance weighting (IVW). Multiple sensitivity analyses were performed to assess the robustness and reliability of the current MR Results. Further confirmatory MR Analysis between COPD and OP was applied. In bibliometrics. Publications were extracted from the Web of Science core collection publications related to osteoporosis and sarcopenia published between January 2014 and October 2024; Bibliometrics and visualization were performed by Microsoft Office Excel, Citespace, and R (Bibliometrix).ResultsThe MR Findings suggest that there is no causal relationship between COPD and BMD at five specific anatomical sites. The results of the primary IVW MR Analysis were generally supported by our sensitivity MR Analysis. We performed MR Analysis for the validation of COPD and OP (IVW OR: 1.019; 95%CI: 0.898-1.564; p = 0.768) also did not support a causal relationship between COPD and BMD. A total of 471 articles written by 1119 organizations from 42 countries/regions by 3331 authors and published in 238 journals were identified in the bibliometric analysis. China is the leading country in terms of the number of publications. China Medical University contributed the most publications. The International Journal of Chronic Obstructive Pulmonary Disease has the highest publication in this field.ConclusionsIn conclusion, This MR Study found no causal relationship between COPD and OP, suggesting that the observed associations may be due to common genetic effects or environmental confounders. The global research trends in this field in the past decade were summarized through bibliometric analysis, and care became the focus of future research on the relationship between copd and OP.

Dataset Information

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

Background

Methods

Results

Conclusion

Publications

Gut microbiota and chronic obstructive pulmonary disease: a Mendelian randomization study.

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