慢性阻塞性肺疾病与房颤及房扑因果关系的孟德尔随机化研究

A Mendelian randomized study on the causal relationship between chronic obstructive pulmonary disease and atrial fibrillation or flutter

目的:采用两样本孟德尔随机化研究方法评估慢性阻塞性肺疾病(慢阻肺)与房颤及房扑发生风险之间的潜在因果关系。方法:研究数据来自全基因组关联研究(GWAS)汇总数据集,其中慢阻肺数据包含3 871例样本,房颤及房扑数据包含5 669例样本,选取17个与慢阻肺密切相关的遗传位点作为工具变量。分别采用逆方差加权、加权中位数和MREgger法进行孟德尔随机化分析。同时采用MR-Egger检测水平多效性,“Leave-one-out”进行敏感性分析保证结果稳健性。结果:逆方差加权法分析结果显示慢阻肺与房颤及房扑发生之间呈显著正相关(OR=1.227,95%CI:1.024~1.470,P=0.027);加权中位数结果显示了相似的因果关系(OR=1.209,95%CI:1.008~1.450,P=0.041)。敏感性分析中MR-Egger检验P=0.65,表明没有水平多效性,Leave-one-out亦未检测到对结果影响大的SNP。结论:慢阻肺与房颤及房扑发生之间可能存在正向因果关系。

Objective To investigate the potential causal relationship between chronic obstructive pulmonary disease(COPD)and the risk of atrial fibrillation/flutter by using a two‑sample Mendelian randomization(MR)approach.Methods The study data were obtained from summary statistics of genome‑wide association studies(GWAS),with 3871 COPD cases and 5669 atrial fibrillation/flutter cases included.A total of seventeen genetic variants that are closely associated with COPD were selected as instrumental variables.MR analysis was carried out by inverse variance weighted,weighted median,and MR‑Egger methods,respectively.MR‑Egger test was used to detect horizontal pleiotropy,and the leave‑one‑out sensitivity analysis was conducted to ensure result robustness.Results The inverse variance weighted analysis showed a significant positive correlation between COPD and the risk of atrial fibrillation/flutter(OR=1.227,95%CI:1.024⁃1.470,P=0.027).The weighted median method produced similar results(OR=1.209,95%CI:1.008⁃1.450,P=0.041).In the sensitivity analysis,the MR‑Egger test with a P‑value of 0.65 suggests the absence of horizontal pleiotropy.Furthermore,the Leave‑one‑out analysis did not identify any influential SNPs significantly affecting the results.Conclusion This study suggests that there may be a positive causal relationship between COPD and the risk of atrial fibrillation/flutter.