基于孟德尔随机化分析胃食管反流病与慢性阻塞性肺疾病的因果关系研究

刘波; 游俊杰; 郑思琳; 黄敏

doi:10.7619/jcmp.20232575

基于孟德尔随机化分析胃食管反流病与慢性阻塞性肺疾病的因果关系研究

刘波^{1, 2},
游俊杰¹,
郑思琳³,
黄敏^2, ,

1.
西南医科大学护理学院, 四川泸州, 646000
2.
西南医科大学附属医院呼吸与危重症医学科, 四川泸州, 646000
3.
西南医科大学附属医院护理部, 四川泸州, 646000

基金项目:

四川省干部保健科研课题资金资助项目川干研2021-1503

详细信息

通讯作者:
黄敏, E-mail: hm20140313@163.com

中图分类号: R562;R571;R319
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- 文章访问数: 215
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- PDF下载量: 17
出版历程
- 收稿日期: 2023-08-13
- 修回日期: 2023-10-30
- 网络出版日期: 2024-01-22
- 刊出日期: 2024-01-14

Causal relationship between gastroesophageal reflux disease and chronic obstructive pulmonary disease based on Mendelian randomization analysis

LIU Bo^{1, 2},
YOU Junjie¹,
ZHENG Silin³,
HUANG Min^2, ,

1.
School of Nursing, Southwest Medical University, Luzhou, Sichuan, 646000
2.
Department ofRespiratory and Critical Care Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000
3.
Nursing Department, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000

摘要

摘要:
目的
基于双向两样本孟德尔随机化(MR)方法分析胃食管反流病(GERD)与慢性阻塞性肺疾病(COPD)的因果关系。

方法
从全基因组关联研究(GWAS)中获取GERD与COPD的遗传变异信息, 并以此作为工具变量。采用逆方差加权法(IVW)、加权中位数法和MR-Egger回归分析法进行MR分析，并通过敏感性分析验证结果的稳健性。

结果
遗传预测的GERD与COPD发生风险具有显著正相关性，而COPD与GERD发生风险无统计学关联。正向IVW结果显示比值比(OR)=1.305 7, 95%置信区间(95%CI)为1.114 4~1.529 8, P=0.000 9; 逆向IVW结果显示OR=0.982 3, 95%CI为0.917 4~1.051 9, P=0.610 4。敏感性分析未发现任何潜在偏倚。

结论
MR分析显示GERD是COPD的一个风险因子，治疗GERD可能有助于预防或延缓COPD的进展。
- 胃食管反流病 /
- 慢性阻塞性肺疾病 /
- 孟德尔随机化 /
- 因果关系 /
- 遗传变异
Abstract:
Objective
To analyze the causal relationship between gastroesophageal reflux disease (GERD) and chronic obstructive pulmonary disease (COPD) based on the bidirectional two-sample Mendelian randomization (MR).

Methods
Genetic variation information of GERD and COPD was obtained from Genome-Wide Association Studies (GWAS) and used as instrumental variables. Inverse variance-weighted (IVW), weighted median and MR-Egger methods were used for MR analysis, and sensitivity analysis was performed to validate the robustness of the results.

Results
A significant positive correlation was observed between genetically predicted GERD and the incidence risk of COPD, but there was no statistical association between COPD and the incidence risk of GERD. Positive IVW result showed that the odds ratio (OR) was 1.305 7, the 95% confidence interval (95%CI) was 1.114 4 to 1.529 8, and the P value was 0.000 9; the reverse IVW result showed that the OR was 0.982 3, the 95%CI was 0.917 4 to 1.051 9, and the P value was 0.610 4. Sensitivity analysis did not find any potential bias.

Conclusion
MR analysis shows that GERD is a risk factor for COPD, and treating GERD may help prevent or delay the progression of COPD.
- gastroesophageal reflux disease /
- chronic obstructive pulmonary disease /
- Mendelian randomization /
- causal relationship /
- genetic variation

HTML全文

图 1 孟德尔随机化分析结果

A: 正向MR分析结果; B: 反向MR分析结果。

下载: 全尺寸图片幻灯片

表 1 工具变量信息

暴露	单核苷酸多态性	效应位点	其他位点	P	Beta	SE	F
COPD	rs11846838	A	G	4.67E-08	0.062 2	0.011 4	29.850 8
	rs12449174	A	G	2.91E-08	0.148 6	0.026 8	30.767 2
	rs13270042	G	A	2.28E-08	0.098 7	0.017 7	31.242 3
	rs28929474	T	C	2.06E-18	0.326 6	0.037 3	76.635 5
	rs3025383	C	T	2.33E-08	-0.084 5	0.015 1	31.195 0
	rs7671167	T	C	1.88E-08	0.062 9	0.011 2	31.611 1
	rs8089390	T	C	2.17E-08	-0.070 4	0.012 6	31.332 0
GERD	rs111472920	T	G	4.47E-08	0.098 7	0.018 0	30.066 9
	rs12706746	A	G	4.24E-09	0.036 9	0.006 3	34.306 1
	rs12939066	T	C	3.13E-11	0.041 5	0.006 2	44.803 6
	rs13167137	T	G	2.82E-08	-0.032 8	0.005 9	30.906 1
	rs1473115	T	C	3.95E-10	0.039 6	0.006 3	39.510 2
	rs15071	T	C	1.01E-08	-0.042 8	0.007 5	32.566 0
	rs1858828	T	G	3.23E-08	0.032 7	0.005 9	30.717 9
	rs3072	T	C	1.86E-08	-0.034 5	0.006 1	31.987 4
	rs62046253	T	C	1.30E-08	-0.035 2	0.006 2	32.233 1
	rs62442944	T	G	3.49E-08	0.041 8	0.007 6	30.250 0
	rs6683411	A	G	4.82E-08	0.032 4	0.005 9	30.156 9
	rs6710685	T	C	1.96E-09	0.039 1	0.006 5	36.184 9
	rs6762606	T	C	4.18E-08	-0.035 9	0.006 5	30.504 4
	rs6809836	A	G	3.70E-09	0.038 3	0.006 5	34.719 3
	rs6991878	T	C	2.71E-08	-0.033 8	0.006 1	30.702 5
	rs72704785	A	G	6.81E-09	0.045 9	0.007 9	33.757 6
	rs7552188	T	C	1.07E-08	0.041 3	0.007 2	32.903 0
	rs769671	T	C	9.28E-10	-0.038 5	0.006 3	37.345 7

下载: 导出CSV

表 2 敏感性分析结果

暴露	结局	SNPs/个	异质性检验		MR-Egger多效性检验		MR-PRESSO离群值检测
暴露	结局	SNPs/个	Q	P	截距值	P	残差平方和	P	离群SNP
GERD	COPD	18	17.926 12	0.393 5	-0.017 9	0.392 7	20.311 47	0.404 9	无
COPD	GERD	7	5.513 072	0.479 9	0.009 4	0.222 2	7.259 081	0.524 4	无
GERD: 胃食管反流病; COPD: 慢性阻塞性肺疾病; SNPs: 单核苷酸多态性; MR-PRESSO: 孟德尔随机多态性残差和离群值。

下载: 导出CSV

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