支气管哮喘与骨密度因果关联的孟德尔随机化分析

刘莲莲; 于会勇; 李磊; 郭雨菲; 聂天旸; 满天; 位式祥; 谢楚溪; 陈天韵; 王成祥

doi:10.7619/jcmp.20241383

支气管哮喘与骨密度因果关联的孟德尔随机化分析

1.
北京中医药大学第三附属医院呼吸科, 北京, 100029
2.
北京中医药大学第三附属医院感染科, 北京, 100029

基金项目:

国家自然科学基金面上项目 82074389

详细信息

通讯作者:
王成祥, E-mail: wang601@vip.sina.com

中图分类号: R562.2;R322.7;R681
计量
- 文章访问数: 185
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- PDF下载量: 19
出版历程
- 收稿日期: 2024-04-06
- 修回日期: 2024-06-10
- 网络出版日期: 2024-07-19
- 刊出日期: 2024-07-27

Mendelian randomization analysis of the causal association between bronchial asthma and bone mineral density

1.
Department of Respiratory Medicine, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029
2.
Department of Infectious Diseases, the Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, 100029

摘要

摘要:
目的
采用两样本孟德尔随机化(MR)方法探讨支气管哮喘与不同部位骨密度的因果关联。
方法
从不同的全基因组关联分析研究中分别获取暴露因素和结局的汇总数据,选取与支气管哮喘强相关的单核苷酸多态性作为工具变量,并去除连锁不平衡者。采用逆方差加权法(IVW)作为MR分析的主要方法,并采用加权中位数法、简单模型、加权模型和MR-Egger回归方法进行补充,通过敏感性分析评估结果的稳定性。
结果
IVW的随机效应模型分析结果显示,跟骨骨密度(OR=0.986,95% CI:0.974~0.998,P=0.023)作为结局数据集,与支气管哮喘存在反向因果效应,腰椎骨密度(OR=1.031,95% CI:0.984~1.081,P=0.195)、股骨颈骨密度(OR=1.014,95% CI:0.973~1.057,P=0.505)、前臂骨密度(OR=1.011,95% CI:0.935~1.094,P=0.775)作为结局数据集,与支气管哮喘无因果效应。MR-Egger截距检验结果显示,腰椎骨密度、股骨颈骨密度、前臂骨密度、跟骨骨密度截距的P>0.05,表明不存在水平多效性,结果较稳定。
结论
MR分析显示支气管哮喘与跟骨骨密度存在反向因果效应,临床医师应加强对支气管哮喘患者跟骨骨密度的监测,以便及时发现并干预骨质疏松症。
- 支气管哮喘 /
- 骨密度 /
- 孟德尔随机化 /
- 遗传变异 /
- 骨质疏松症
Abstract:
Objective
To investigate the causal association between bronchial asthma and bone mineral density at different sites using a two-sample Mendelian randomization (MR) approach.
Methods
Summary data for exposure factors and outcome were obtained from different genome-wide association studies.Single nucleotide polymorphisms strongly associated with bronchial asthma were selected as instrumental variables,and those in linkage disequilibrium were excluded.The inverse-variance weighted (IVW) method was used as the primary method for MR analysis,complemented by weighted median,simple mode,weighted mode,and MR-Egger regression methods.Sensitivity analyses were conducted to assess the stability of the results.
Results
The random-effects model of IVW analysis showed that heel bone mineral density (OR=0.986;95% CI,0.974 to 0.998;P=0.023) as the outcome dataset had a reverse causal effect with bronchial asthma,while lumbar spine bone mineral density (OR=1.031;95% CI,0.984 to 1.081;P=0.195),femoral neck bone mineral density (OR=1.014;95% CI,0.973 to 1.057;P=0.505),and forearm bone mineral density (OR=1.011;95% CI,0.935 to 1.094;P=0.775) as outcome datasets showed no causal effect with bronchial asthma.The MR-Egger intercept test results indicated that the P-values for the intercepts of lumbar bone mineral density,femoral neck bone mineral density,forearm bone mineral density,and calcaneal bone mineral density were all over 0.05,suggesting no horizontal pleiotropy and relatively stable results.
Conclusion
MR analysis reveals a reverse causal effect between bronchial asthma and heel bone mineral density,suggesting that clinicians should strengthen the monitoring of heel bone mineral density in patients with bronchial asthma to timely detect and intervene osteoporosis.
- bronchial asthma /
- bone mineral density /
- Mendelian randomization /
- genetic variation /
- osteoporosis

HTML全文

图 1 支气管哮喘对不同部位骨密度影响的孟德尔随机化分析留一法敏感性分析图

下载: 全尺寸图片幻灯片

图 2 支气管哮喘对不同部位骨密度影响的孟德尔随机化分析漏斗图

下载: 全尺寸图片幻灯片

表 1 GWAS汇总数据信息

暴露因素/结局	数据公布年份	样本种族来源	单核苷酸多态性数量/个	样本量/例	数据来源网址	PubMed ID
支气管哮喘	2021	欧洲	34 551 291	408 442	https://www.ebi.ac.uk/gwas/downloads/summary-statistics	34103634
腰椎骨密度	2015	混合	10 582 867	28 498	http://www.gefos.org/?q=content/data-release-2015	26367794
股骨颈骨密度	2015	混合	10 586 900	32 735	http://www.gefos.org/?q=content/data-release-2015	26367794
前臂骨密度	2015	混合	9 955 366	8 143	http://www.gefos.org/?q=content/data-release-2015	26367794
跟骨骨密度	2018	欧洲	13 705 641	426 824	http://www.gefos.org/?q=content/data-release-2018	30598549

下载: 导出CSV

表 2 支气管哮喘与骨密度关系的孟德尔随机化分析结果

暴露因素	结局	单核苷酸多态性数量/个	孟德尔随机化分析
暴露因素	结局	单核苷酸多态性数量/个	方法	OR	95%CI	P
支气管哮喘	腰椎骨密度	57	MR-Egger回归	1.127	1.004~1.264	0.047
			加权中位数法	1.023	0.957~1.093	0.491
			逆方差加权法	1.031	0.984~1.081	0.195
			简单模型	1.014	0.883~1.164	0.843
			加权模型	1.056	0.954~1.169	0.258
支气管哮喘	股骨颈骨密度	57	MR-Egger回归	1.039	0.936~1.152	0.479
			加权中位数法	1.021	0.965~1.079	0.489
			逆方差加权法	1.014	0.973~1.057	0.505
			简单模型	0.989	0.886~1.104	0.850
			加权模型	1.029	0.957~1.106	0.449
支气管哮喘	前臂骨密度	57	MR-Egger回归	1.027	0.843~1.252	0.792
			加权中位数法	1.066	0.960~1.183	0.252
			逆方差加权法	1.011	0.935~1.094	0.775
			简单模型	1.022	0.832~1.255	0.826
			加权模型	1.058	0.918~1.220	0.459
支气管哮喘	跟骨骨密度	49	MR-Egger回归	0.982	0.952~1.012	0.237
			加权中位数法	0.985	0.970~1.001	0.071
			逆方差加权法	0.986	0.974~0.998	0.023
			简单模型	0.975	0.936~1.015	0.188
			加权模型	0.975	0.944~1.007	0.153

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表 3 敏感性分析结果

暴露因素	结局	异质性检验		水平多效性检验
暴露因素	结局	Q	P	截距	P
支气管哮喘	腰椎骨密度	73.709	0.056	-0.007	0.107
	股骨颈骨密度	76.945	0.033	-0.002	0.627
	前臂骨密度	64.274	0.209	-0.001	0.869
	跟骨骨密度	85.505	0.001	< 0.001	0.754

下载: 导出CSV

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