Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD...Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and 展开更多
目的采用两样本孟德尔随机化(MR)探讨417种循环代谢产物与吉兰-巴雷综合征(GBS)风险的因果关系。方法通过MRC IEU OpenGWAS项目获得3个循环代谢产物全基因组关联研究(GWAS)数据,分别为“met-a”“met-c”和“met-d”。GBS相关的单核苷...目的采用两样本孟德尔随机化(MR)探讨417种循环代谢产物与吉兰-巴雷综合征(GBS)风险的因果关系。方法通过MRC IEU OpenGWAS项目获得3个循环代谢产物全基因组关联研究(GWAS)数据,分别为“met-a”“met-c”和“met-d”。GBS相关的单核苷酸多态性位点(SNPs)数据来源于芬兰生物银行数据库,表型代码为“finn-b-G6_GUILBAR”。将来自GWAS的与循环代谢产物密切相关的遗传变异数据(SNPs)作为工具变量(IVs),与来自芬兰的GBS GWAS数据进行双样本MR分析,主要采用随机效应模型的逆方差加权(IVW)方法,根据效应指标优势比(OR)和95%CI评估结果。使用留一法、异质性检验、水平基因多效性检验验证结果的稳定性和可靠性。结果共5种循环代谢产物具有与GBS因果关系的提示性证据。其中,肌酐(OR=2.924,95%CI:1.194~7.163,P=0.019)、谷氨酰胺(OR=1.902,95%CI:1.007~3.592,P=0.048)、异戊酰基肉碱(OR=140.767,95%CI:3.510~5645.336,P=0.009)的循环水平与GBS风险较高有关。相反,基因预测葡萄糖(OR=0.308,95%CI:0.010~0.981,P=0.046)、X-11491(OR=0.069,95%CI:0.007~0.707,P=0.024)的循环水平与GBS风险呈负相关。结论肌酐、谷氨酰胺、异戊酰基肉碱、葡萄糖、X-11491可能与GBS有因果关系。展开更多
文摘Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and
文摘目的采用两样本孟德尔随机化(MR)探讨417种循环代谢产物与吉兰-巴雷综合征(GBS)风险的因果关系。方法通过MRC IEU OpenGWAS项目获得3个循环代谢产物全基因组关联研究(GWAS)数据,分别为“met-a”“met-c”和“met-d”。GBS相关的单核苷酸多态性位点(SNPs)数据来源于芬兰生物银行数据库,表型代码为“finn-b-G6_GUILBAR”。将来自GWAS的与循环代谢产物密切相关的遗传变异数据(SNPs)作为工具变量(IVs),与来自芬兰的GBS GWAS数据进行双样本MR分析,主要采用随机效应模型的逆方差加权(IVW)方法,根据效应指标优势比(OR)和95%CI评估结果。使用留一法、异质性检验、水平基因多效性检验验证结果的稳定性和可靠性。结果共5种循环代谢产物具有与GBS因果关系的提示性证据。其中,肌酐(OR=2.924,95%CI:1.194~7.163,P=0.019)、谷氨酰胺(OR=1.902,95%CI:1.007~3.592,P=0.048)、异戊酰基肉碱(OR=140.767,95%CI:3.510~5645.336,P=0.009)的循环水平与GBS风险较高有关。相反,基因预测葡萄糖(OR=0.308,95%CI:0.010~0.981,P=0.046)、X-11491(OR=0.069,95%CI:0.007~0.707,P=0.024)的循环水平与GBS风险呈负相关。结论肌酐、谷氨酰胺、异戊酰基肉碱、葡萄糖、X-11491可能与GBS有因果关系。
