支气管哮喘与骨密度因果关联的孟德尔随机化分析

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

  • 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。

     

    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.

     

/

返回文章
返回