体重指数在阻塞性睡眠呼吸暂停和高血压关联中的中介效应：一项孟德尔随机化研究

Mediating effects of body mass index on the association between obstructive sleep apnea and hypertension：a Mendelian randomization study

    摘要
  • 摘要:
    目的 应用双样本多变量孟德尔随机化研究方法评估体重指数在阻塞性睡眠呼吸暂停（OSA）与高血压的潜在因果关联中的中介效应。
    方法 使用公开发布的全基因组关联研究汇总统计数据进行单变量和多变量孟德尔随机化（MR）分析，以估计OSA与高血压的因果关联及体重指数的中介效应。采用逆方差加权（IVW）、加权中值估计模型（WME）、基于加权模型的方法（WM）、MR-Egger回归模型和简单众数法（SM）进行效应估计。基于IVW方法以及孟德尔随机化多效性残差与离群值分析（MR-PRESSO）对研究的异质性和多效性进行检测。
    结果 单变量MR分析结果提示，OSA和体重指数与高血压关联的比值比（OR）值分别为1.291（95%CI：1.111～1.500）和1.981（95%CI：1.841～2.132）；多变量MR结果显示，OSA与高血压的关联OR值为1.051（95%CI：0.943～1.173）。进一步分析体重指数在OSA与高血压关联中存在中介作用，其中介效应为0.09，比例为34.6%（Sobel检验，P＜0.001）。
    结论 OSA和体重指数与高血压存在因果关联，中介分析发现，BMI是OSA与高血压关联中重要的中介因子并可增加高血压发生风险。

     

    Abstract:
    Objective This study aims to evaluate the mediating effects of body mass index (BMI) on the association between obstructive sleep apnea (OSA) and hypertension using a two-sample multivariate Mendelian randomization (MR) study method.
    Methods Summary statistics from publicly available genome-wide association studies were used for univariate and multivariate MR analyses to estimate the causal relationships and mediating effects of BMI. The inverse variance weighted (IVW) method was used as the main method for effect estimation, with additional methods including weighted median (WME), weighted mode (WM), MR-Egger regression, and simple mode method (SM). Heterogeneity and pleiotropy in the study were assessed using the IVW method and pleiotropy residual and outlier analysis in Mendelian randomization (MR-PRESSO).
    Results The odds ratios (ORs) from univariate MR analyses regarding OSA and BMI on hypertension were 1.291 (95%CI: 1.111 to 1.500) and 1.981 (95%CI: 1.841 to 2.132) respectively. The multivariable MR analysis showed that the odds ratio for the association between OSA and hypertension was 1.051 (95%CI: 0.943 to 1.173). Further analysis indicated that BMI played a mediating role on the relationship between OSA and hypertension, with a mediation effect of 0.09 and a proportion of 34.6% (sobel-test, P＜0.001).
    Conclusion OSA is a risk factor of hypertension and BMI had a mediating effect on the association.

     

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