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一项双向孟德尔随机化研究,探究强直性脊柱炎与慢性阻塞性肺疾病之间的因果关系。

A Bidirectional Mendelian Randomization Study Investigating the Causal Relationship Between Ankylosing Spondylitis and Chronic Obstructive Pulmonary Disease.

作者信息

Pan Di, Dai Xiaoling, Li Pan, Xue Luan

机构信息

Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2025 Feb 8;20:259-271. doi: 10.2147/COPD.S491579. eCollection 2025.

Abstract

BACKGROUND

Previous studies have found an association between ankylosing spondylitis (AS) and chronic obstructive pulmonary disease (COPD); however, no research has investigated this relationship using Mendelian randomization (MR).

METHODS

This study employed a bidirectional two-sample MR approach to assess the causal connection between AS and COPD. The analysis utilized publicly available statistics on AS and COPD from the Genome-wide Association Study (GWAS). The primary MR method employed was Inverse-Variance Weighting (IVW), supplemented by additional MR methods such as weighted median, MR-Egger, simple mode, and weighted mode. Sensitivity analyses were also performed to evaluate the impact of heterogeneity and pleiotropy on the MR results.

RESULTS

The study included two datasets related to AS (ebi-a-GCST005529 and ukb-a-88) and two datasets related to COPD (ebi-a-GCST90018807 and finn-b-J10_COPD). In our forward MR, the analysis of ebi-a-GCST005529 dataset against ebi-a-GCST90018807 dataset showed that AS was associated with an increased risk of COPD ( = 1.1326, = 1.0181-1.2600, = 0.0221). However, there was no causal relationship between AS and COPD in the rest of the dataset analyses. In reverse MR analysis, no causal effect between COPD and AS was found among the datasets.

CONCLUSION

Our research provided partial evidence to support the viewpoint that AS may increase the prevalence of COPD. AS may be a risk factor for COPD, however, further studies are needed to validate these results and elucidate the underlying mechanisms.

摘要

背景

先前的研究发现强直性脊柱炎(AS)与慢性阻塞性肺疾病(COPD)之间存在关联;然而,尚无研究使用孟德尔随机化(MR)来调查这种关系。

方法

本研究采用双向双样本MR方法来评估AS与COPD之间的因果关系。分析利用了全基因组关联研究(GWAS)中关于AS和COPD的公开可用统计数据。采用的主要MR方法是逆方差加权(IVW),并辅以加权中位数、MR-Egger、简单模式和加权模式等其他MR方法。还进行了敏感性分析,以评估异质性和多效性对MR结果的影响。

结果

该研究包括两个与AS相关的数据集(ebi-a-GCST005529和ukb-a-88)以及两个与COPD相关的数据集(ebi-a-GCST90018807和finn-b-J10_COPD)。在我们的正向MR中,对ebi-a-GCST005529数据集与ebi-a-GCST90018807数据集的分析表明,AS与COPD风险增加相关(比值比=1.1326,95%置信区间=1.0181-1.2600,P=0.0221)。然而,在其余数据集分析中,AS与COPD之间未发现因果关系。在反向MR分析中,各数据集中未发现COPD与AS之间存在因果效应。

结论

我们的研究提供了部分证据支持AS可能增加COPD患病率的观点。AS可能是COPD的一个危险因素,然而,需要进一步研究来验证这些结果并阐明潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c160/11818834/0fd77042db12/COPD-20-259-g0001.jpg

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