An approach to estimate bidirectional mediation effects with application to body mass index and fasting glucose.
An approach to estimate bidirectional mediation effects with application to body mass index and fasting glucose.
复制标题
一种应用体重指数和空腹血糖来估计双向中介效应的方法。
DOI：
10.1111/ahg.12261
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发表时间：
2018
影响因子：
1.9
通讯作者：
Shete,Sanjay
中科院分区：
文献类型：
--
作者：
Talluri,Rajesh;Shete,Sanjay
肥胖和2型糖尿病是已知相互依赖的主要公共卫生问题。遗传变异已与肥胖，2型糖尿病，或两者兼而有之;因此，我们假设，一些单核苷酸多态性（SNP）与这两种条件可能是通过肥胖介导的影响2型糖尿病，反之亦然。我们提出了一个双向中介分析的框架。仿真结果表明，这种方法准确地估计参数，无论是单向或双向的调解。在许多情况下，当中介变量对初始变量进行回归，结果对中介变量和初始变量进行回归时，由于模型中没有其他未测量的协变量，因此所得残差是相关的。我们表明，该模型在这种情况下提供了准确的估计，太。我们应用所提出的方法，使用来自动脉粥样硬化多种族研究队列的遗传数据，研究与2型糖尿病和肥胖相关的SNP的介导作用。具体来说，我们使用体重指数（BMI）作为衡量肥胖的指标，空腹血糖作为衡量2型糖尿病的指标。我们评估了与BMI和空腹血糖相关的前6个SNP。两个SNPs（rs3752355和rs6087982）通过空腹血糖对BMI有间接影响[分别为0.2677; 95%置信区间（CI）（0.0007，0.6548）和0.3301; 95% CI（0.0881，0.8544）]。其余四个SNP（rs7969190、rs 4869710、rs 10201400和rs 12421620）直接影响BMI和空腹血糖，而没有介导作用。
Obesity and type 2 diabetes are major public health issues with known interdependence. Genetic variants have been associated with obesity, type 2 diabetes, or both; thus, we hypothesize that some single nucleotide polymorphisms (SNPs) associated with both conditions may be mediated through obesity to affect type 2 diabetes or vice versa. We propose a framework for bidirectional mediation analyses. Simulations show that this approach accurately estimates the parameters, whether the mediation is unidirectional or bidirectional. In many scenarios, when the mediator is regressed on the initial variable and the outcome is regressed on the mediator and the initial variable, the resulting residuals are correlated because of other unmeasured covariates not in the model. We show that the proposed model provides accurate estimates in this scenario, too. We applied the proposed approach to investigate the mediating effects of SNPs associated with type 2 diabetes and obesity using genetic data from the Multi‐Ethnic Study of Atherosclerosis cohort. Specifically, we used body mass index (BMI) as a measure for obesity and fasting glucose as a measure for type 2 diabetes. We evaluated the top 6 SNPs associated with both BMI and fasting glucose. Two SNPs (rs3752355 and rs6087982) had indirect effects on BMI mediated through fasting glucose [0.2677; 95% confidence interval (CI) (0.0007, 0.6548) and 0.3301; 95% CI (0.0881, 0.8544), respectively]. The remaining four SNPs (rs7969190, rs4869710, rs10201400, and rs12421620) directly affect BMI and fasting glucose without mediating effects.