Dataset Information

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

ABSTRACT:

Objective

Observational studies have reported that chronic obstructive pulmonary disease (COPD) is often accompanied by autoimmune diseases, but the causal relationships between them remain uncertain. In this Mendelian study, we aimed to investigate the potential causal relationship between COPD and four common autoimmune diseases.

Methods

We conducted an analysis of summary data on COPD and autoimmune disease using publicly available genome-wide association studies (GWAS) summary data. We initially employed the inverse- variance weighted method as the primary approach to establish the causal impact of COPD on autoimmune diseases in the sample and conducted additional sensitivity analyses to examine the robustness of the results. Subsequently, we performed reverse Mendelian randomization (MR) analyses for the four autoimmune diseases. Finally, the potential for bidirectional causal relationships was assessed.

Results

Our MR analysis revealed no significant causal relationship between COPD and any of the studied autoimmune diseases. However, reverse MR results indicated a significant association between rheumatoid arthritis (RA), osteoarthritis (OA) and the risk of developing COPD, with respective odds ratios (OR) of 377.313 (95% CI, 6.625-21487.932, P = 0.004) for RA and 11.097 (95% CI, 1.583-77.796, P = 0.015) for OA. Sensitivity analyses confirmed the robustness of the results.

Conclusion

Our findings support a potential causal relationship between autoimmune diseases and COPD, highlighting the importance of considering comorbidities in clinical management of COPD.

SUBMITTER: Yu X

PROVIDER: S-EPMC10949139 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Yu Xiaohui X Cheng Xue X Lv Lin L Wang Na N Li Mengcong M Ji Wenwen W Liu Tingting T Wang Guangdong G Hu Tinghua T Shi Zhihong Z

Frontiers in medicine 20240305

<h4>Objective</h4>Observational studies have reported that chronic obstructive pulmonary disease (COPD) is often accompanied by autoimmune diseases, but the causal relationships between them remain uncertain. In this Mendelian study, we aimed to investigate the potential causal relationship between COPD and four common autoimmune diseases.<h4>Methods</h4>We conducted an analysis of summary data on COPD and autoimmune disease using publicly available genome-wide association studies (GWAS) summary ...[more]

PMID: 38504914

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Project description:BackgroundChronic 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.MethodsWe 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.ResultsPreliminary 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.ConclusionsOur 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.

Project description:BackgroundAutoimmune diseases (ADs) are a category of conditions characterized by misrecognition of autologous tissues and organs by the immune system, leading to severe impairment of patients' health and quality of life. Increasing evidence suggests a connection between fluctuations in plasma metabolites and ADs. However, the existence of a causal relationship behind these associations remains uncertain.MethodsApplying the two-sample mendelian randomization (MR) method, the reciprocal causality between plasma metabolites and ADs was analyzed. We took the intersection of two metabolite genome-wide association study (GWAS) datasets for GWAS-meta and obtained 1,009 metabolites' GWAS data using METAL software. We accessed GWAS summary statistics for 5 common ADs, inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) from published GWAS data. MR analyses were performed in discovery and replication stage simultaneously. Meanwhile, the reverse MR analysis was conducted to investigate the possibility of reverse causal association. Furthermore, a series of sensitivity analyses were conducted to validate the robustness of the results. These statistical analyses were conducted using R software. Finally, the web version of MetaboAnalyst 5.0. was applied to analyze metabolic pathways. Ultimately, we conducted ELISA assays on plasma samples from patients to validate the results.Results4 metabolites were identified to have causal relationships with IBD, 2 metabolites with MS, 13 metabolites with RA, and 4 metabolites with T1D. In the reverse MR analysis, we recognized causality between SLE and 22 metabolites, IBD and 4 metabolites, RA and 22 metabolites, and T1D and 37 metabolites. Additionally, 4 significant metabolic pathways were identified in RA by metabolic pathway analysis in the forward MR analysis. Correspondingly, in the reverse, 11 significant metabolic pathways in RA, 8 in SLE, and 4 in T1D were obtained using identical approaches. Furthermore, the protective role of glutamate was confirmed through ELISA assays.ConclusionsOur research established a reciprocal causality between plasma metabolites and ADs. Furthermore, diverse metabolic pathways correlated with ADs were uncovered. Novel insights into the prediction and diagnosis were provided, as well as new targets for precise treatment of these conditions were discovered.

Project description:Cysteine cathepsins are proteolytic enzymes crucial in various physiological and pathological processes, primarily operating within lysosomes. Their functions include protein degradation, immune system regulation, and involvement in various diseases. While some cysteine cathepsins play important roles in the immune system, their connection to autoimmune diseases remains unclear. This study proposes using Mendelian randomization to explore the causal relationship between cysteine cathepsins and autoimmune diseases. Single nucleotide polymorphisms (SNPs) for cysteine cathepsins were obtained from a publicly available genome-wide association study (GWAS) dataset, while outcome SNP data were sourced from 10 separate GWAS datasets. Mendelian randomization (MR) analysis employed the Wald ratio (WR) and inverse variance weighted (IVW) approach as primary methods, supplemented by the weighted median and MR-Egger methods. Heterogeneity was assessed using Cochran Q test, and sensitivity analysis was conducted using the MR-PRESSO method. The association strength between exposure and outcome was evaluated using odds ratios (OR) with 95% confidence intervals (CI). The study identified a potential positive correlation between elevated cathepsin B and psoriasis (Wald ratio OR = 1.449, 95% CI: 1.053-1.993, P = .0227). Elevated cathepsin F was potentially linked to ulcerative colitis (WR OR = 1.073, 95% CI: 1.021-1.127, P = .0056), ankylosing spondylitis (WR OR = 1.258, 95% CI: 1.082-1.463, P = .0029), and primary biliary cholangitis(PBC) (WR OR = 1.958, 95% CI: 1.326-2.889, P = .0007). Conversely, cathepsin H appeared protective against celiac disease (WR OR = 0.881, 95% CI: 0.838-0.926, P = 6.5e-7), though elevated levels may increase the risk of type 1 diabetes (IVW OR = 1.121, 95% CI: 1.053-1.194, P = .0003) and PBC (WR OR = 1.792, 95% CI: 1.062-3.024, P = .0288). Cathepsin Z was also associated with an increased risk of type 1 diabetes (IVW OR = 1.090, 95% CI: 1.006-1.181, P = .0349). The MR analysis suggests potential risks of cathepsin B with psoriasis, cathepsin F with ulcerative colitis, ankylosing spondylitis, and PBC, and cathepsin Z with type 1 diabetes. Conversely, cathepsin H may protect against celiac disease but could increase the risk of type 1 diabetes and PBC.

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.

Project description:BackgroundChronic Obstructive Pulmonary Disease (COPD) currently ranks as the third leading cause of mortality worldwide, imposing substantial burdens on societal and individual health. Amongst health research tools, walking pace (WP) and hand grip strength (HGS) are cornerstones, extensively associated with diverse health conditions. However, the intricate interplay between these factors and COPD risk remains ambiguous. This study aims to elucidate the causal association of WP, HGS, with COPD risk through a bidirectional Mendelian randomization (MR) approach.MethodsBidirectional MR analysis was performed using Genome-wide association study (GWAS) data of European individuals for WP, HGS, and COPD. Inverse Variance Weighted (IVW) served as the primary MR analysis approach. To supplement the IVW findings, four additional MR methods [MR-Egger, weighted median, maximum likelihood, simple median] were used. To assess heterogeneity and pleiotropy, sensitivity analyses were performed. In addition, multivariate MR (MVMR) analysis was used to assess causality after adjustment for potential confounders.ResultsIVW method results show a significant negative association between WP and COPD risk in both initial (genome-wide threshold, odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.09-0.51, P = 5.06 × 10- 4) and secondary (locus-wide threshold, OR = 0.27, 95%CI: 0.18-0.41, P = 4.88 × 10- 10) MR analysis. The reverse MR analysis suggested that COPD also diminishes WP. Additionally, a causal risk reduction for COPD with right HGS (OR = 0.74, 95% CI: 0.58-0.94, P = 1.44 × 10- 2) was only found in secondary MR analysis. The outcomes of the four additional MR methods also suggested similar causal relationships, and sensitivity analyses endorsed their robustness. Lastly, the MVMR analysis demonstrated that the WP's effect on reducing COPD risk persisted independently of potential confounding variables.ConclusionA bidirectional causal relationship exists between typical WP and COPD risk. Conversely, a decrease in right HGS is unidirectionally associated with an increased risk of COPD. The study suggests that WP may serve as a predictive factor for COPD or as a simple evaluative indicator for prognosis.

Project description:Several observational studies have revealed an association between autoimmune diseases (AIDs) and colorectal cancer (CRC), although their causal association remained controversial. Therefore, our study used a two-sample Mendelian randomization (MR) analysis to verify the causal association between AIDs and CRC. We employed three common MR approaches, including inverse variance weighted (IVW), weighted median, and MR-Egger methods, to assess the causal association between type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, psoriasis, multiple sclerosis, juvenile idiopathic arthritis, celiac disease, and primary sclerosing cholangitis (PSC) and CRC. The reverse MR analysis was performed to assess the possibility of reverse causation. To evaluate the validity of the analysis, we also performed sensitivity analysis, such as the heterogeneity test, the horizontal pleiotropy test, and the leave-one-out sensitivity analysis, and validated the results in the validation cohort. Our results showed that genetically predicted T1D was nominally associated with a lower risk of CRC (IVW OR = 0.965, 95% CI = 0.939-0.992, P = 0.012). However, genetic susceptibility to psoriasis nominally increased the risk of CRC (IVW OR = 1.026, 95% CI = 1.002-1.050, P = 0.037). Genetically predicted PSC had a significant causal effect on the increasing risk of CRC (IVW OR = 1.038, 95% CI = 1.016-1.060, P = 5.85 × 10-4). Furthermore, the MR analysis between PSC and the CRC validation cohort indicated consistent results. We found no causal association between genetically predicted other five AIDs and CRC (P > 0.05). The results of reverse MR analysis showed that genetically predicted CRC had no causal effect on T1D, psoriasis, and PSC (P > 0.05). The sensitivity analysis demonstrated that the results of the MR analysis were reliable. Our findings help to understand the causal association between AIDs and CRC, which deserves further investigation.

Dataset Information

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Objective

Methods

Results

Conclusion

Publications

The association between chronic obstructive pulmonary disease and autoimmune diseases: a bidirectional Mendelian randomization study.

Similar Datasets

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