JOINT SIGNIFICANCE TESTS FOR MEDIATION EFFECTS OF SOCIOECONOMIC ADVERSITY ON ADIPOSITY VIA EPIGENETICS
JOINT SIGNIFICANCE TESTS FOR MEDIATION EFFECTS OF SOCIOECONOMIC ADVERSITY ON ADIPOSITY VIA EPIGENETICS
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DOI：
10.1214/17-aoas1120
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发表时间：
2018-09-01
影响因子：
1.8
通讯作者：
Huang, Yen-Tsung
中科院分区：
文献类型：
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作者：
Huang, Yen-Tsung
中介分析已成为生物医学研究中的一种流行方法。我们进行中介分析，以调查表观遗传变异是否介导社会经济劣势对肥胖的影响。中介效应可以表示为两个参数的乘积：一个是暴露-中介关联，另一个是以暴露为条件的中介-结果关联。在多中介模型下，我们研究了分别检验两个参数的联合显著性检验，并与广泛使用的关注两个参数乘积的产品显著性检验进行了比较。产品显著性检验的正态近似取决于效应大小和样本量。我们证明联合显著性检验是大小为a的交叉联合检验，并且渐近地比基于正态性的产品显著性检验更强大。基于理论结果，我们构建了基于基因的中介分析和路径特异性分析的强大测试程序。17号染色体基于位点和基因的中介分析的模拟和结果支持联合显著性检验的优势。我们的分析表明，FASN基因的甲基化介导了社会经济逆境对肥胖的影响。
Mediation analysis has become a popular practice in biomedical research. We conduct mediation analyses to investigate whether epigenetic variations mediate the effect of socioeconomic disadvantage on adiposity. Mediation effects can be expressed as a product of two parameters: one for the exposure-mediator association and the other for the mediator-outcome association conditional on the exposure. Under multi-mediator models, we study joint significance tests which examine the two parameters separately and compare with the widely used product significance tests which focus on the product of two parameters. Normal approximation of product significance tests depends on both effect size and sample size. We show that joint significance tests are intersection-union tests with size a and asymptotically more powerful than the normality-based product significance tests. Based on the theoretical results, we construct powerful testing procedures for gene-based mediation analyses and path-specific analyses. Advantage of joint significance tests is supported by simulation as well as the results of locus-based and gene-based mediation analyses of chromosome 17. Our analyses suggest that methylation of FASN gene mediates the effect of socioeconomic adversity on adiposity.