血清尿酸与COPD和肺通气关系的孟德尔随机化研究

严镓文; 吉郡珠; 韩瑞婷; 余海滨

doi:10.16766/j.cnki.issn.1674-4152.003863

血清尿酸与COPD和肺通气关系的孟德尔随机化研究

doi: 10.16766/j.cnki.issn.1674-4152.003863

严镓文^{1, 2},
吉郡珠^{1, 2},
韩瑞婷¹,
余海滨^{1, 2, ,}

1.
河南中医药大学第一附属医院呼吸科, 河南郑州 450003
2.
河南中医药大学呼吸疾病中医药防治省部共建协同创新中心, 河南郑州 450046

基金项目:

河南省中医药科学研究专项课题 2021JDZX005

河南省中医药科学研究专项课题 2022ZYZD04

郑州市协同创新中心专项 2023XTCX043

详细信息

通讯作者:
余海滨，E-mail：yhbzzz@163.com

中图分类号: R563
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- 被引次数: 0
出版历程
- 收稿日期: 2024-01-24
- 网络出版日期: 2025-03-27

Association of uric acid with COPD and pulmonary ventilation based on Mendelian randomization method

YAN Jiawen^{1, 2},
JI Junzhu^{1, 2},
HAN Ruiting¹,
YU Haibin^{1, 2
, ,}

1.
Department of Respiratory Medicine, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan 450003, China

摘要

摘要: 目的相关研究提出了血尿酸(UA)与慢性阻塞性肺疾病及肺通气阻塞的发生发展之间的联系, 本研究采用孟德尔随机化分析方法进一步探讨它们之间的因果关系。方法从全基因组关联研究汇总数据中筛选与COPD、血尿酸、肺通气相关的基因位点, 将其作为工具变量, 分别使用IVW等多种分析方法进行孟德尔随机化分析, 采用MR-PRESSO、MR-Egger截距法、leave-one-out法对相关基因位点进行敏感性分析。结果 IVW结果显示: UA与COPD发生之间不存在因果关系(OR = 1. 053, 95% CI: 0. 932 ~ 1. 189, P = 0. 406), 且MR-PRESS和MREgger均未观察到水平多效性和异质性。UA与第一秒用力呼气容积实测值与预计值的比值(FEV₁%)改变之间无因果关系(β = -0. 006, P = 0. 686), UA与一秒率(FEV₁ / FVC)改变之间无因果关系(β = -0. 004, P = 0. 323), MRPRESSO和MR-Egger观察到水平多效性和异质性, 但对存在水平多效性的基因位点进行剔除后, 结果依然无显著关联(UA-FEV₁% P = 0. 412, UA-FEV₁ / FVC P = 0. 303), 利用留一法对相关基因位点进行逐个剔除后没有观察到上述因果关系发生显著变化。结论本研究结果表明, UA与COPD发生呈正相关关系, 与FEV₁%、FEV₁ / FVC改变之间呈负相关关系, 但均无显著的因果关系。
- 慢性阻塞性肺疾病 /
- 孟德尔随机化 /
- 肺通气 /
- 第一秒呼气容积 /
- 一秒率 /
- 因果关系 /
- 工具变量
Abstract: Objective Relevant studies have indicated a correlation between blood uric acid (UA) levels and the occurrence and progression of chronic obstructive pulmonary disease (COPD) and pulmonary obstruction; In this study, Mendelian randomization analysis is used to further explore the causal relationship between them. Methods The gene loci related to COPD, blood uric acid, and pulmonary ventilation were screened from the aggregated data of genome-wide association studies and used as instrumental variables to conduct Mendelian randomization analysis using various analysis methods such as IVW. MR-PRESSO, MR-Egger intercept and, leave-one-out methods were used to analyze the sensitivity of relevant gene loci. Results IVW results showed no causal relationship between UA and the occurrence of COPD (OR = 1. 053, 95% CI: 0. 932-1. 189, P = 0. 406), and neither MR-PRESSO nor MR-Egger observed horizontal polymorphism and heterogeneity. No significant association between UA and first second forced expiratory volume ratio of the measured value to the predicted value (FEV₁%) changes (β = -0. 006, P = 0. 686), No significant association between UA and FEV₁ / forced vital capacity (FVC) changes (β = -0. 004, P = 0. 323), and horizontal polymorphism and heterogeneity were observed for MRPRESSO and MR-Egger, however, after excluding SNPs with horizontal pleiotropy, the results still showed no significant association (UA-FEV₁% P = 0. 412, UA-FEV₁ / FVC P = 0. 303). No significant changes in the above causal relationships were observed after the relevant gene loci were removed one by one by the leave-one-out method. Conclusion The results of this study show that UA is positively correlated with the development of COPD and negatively correlated with changes in FEV 1% and FEV₁ / FVC, but none of these is a correlate causal relationship.
- Chronic obstructive pulmonary disease /
- Mendelian randomization /
- Pulmonary ventilation /
- First second forced expiratory volume /
- First second forced expiratory volume / forced vital capacity /
- Causality /
- Instrumental variables

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图 1 工具变量的3个核心假设

Figure 1. Three core assumptions of IVs

下载: 全尺寸图片幻灯片

图 2 UA与COPD之间MR分析结果散点图

注：A表示UA与COPD之间MR分析散点图；B表示UA与COPD之间MR分析森林图

Figure 2. Scatter plot of MR Analysis results between UA and COPD

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图 3 UA与FEV₁%和FEV₁/FVC之间MR分析结果散点图

注：A表示UA与FEV₁%之间MR分析结果散点图、B表示UA与FEV₁/FVC之间MR分析结果散点图。

Figure 3. Scatter plot of MR Analysis results between UA and FEV₁% and FEV₁/FVC

下载: 全尺寸图片幻灯片

图 4 留一法检验结果

注：A为UA-COPD；B为UA-FEV₁%；C为UA-FEV₁/FVC。

Figure 4. Results of leave-one-out cross-validation

下载: 全尺寸图片幻灯片

表 1 本研究所选取的GWAS数据简要信息

Table 1. Summary of the GWAS included in this two-simple MR study

变量	ID	样本量(人)	SNP (个)	性别	年份
UA	bbj-a-57	109 029	6 108 953	男、女	2019
COPD	finn-b-J10_COPD	193 638	16 380 382	男、女	2021
FEV₁%	ukb-b-13405	148 653	9 851 867	男、女	2018
FEV₁/FVC	ieu-b-106	55 907	12 321 875	男、女	2021

下载: 导出CSV

表 2 UA与COPD之间MR分析结果

Table 2. Results of MR Analysis between UA and COPD

MR方法	N(SNPs)	效应值β	SE	P值	OR(95% CI)
MR Egger	39	0.007	0.104	0.946	1.007(0.822~1.234)
Weighted median	39	-0.016	0.083	0.844	0.984(0.837~1.157)
IVW	39	0.051	0.062	0.406	1.053(0.932~1.189)

下载: 导出CSV

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