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Meta-Analysis of SNP-Environment Interaction with Heterogeneity
Human Heredity ( IF 1.8 ) Pub Date : 2019-12-19 , DOI: 10.1159/000504170
Qinqin Jin 1, 2 , Gang Shi 3
Affiliation  

Meta-analyses are widely used in genome-wide association studies to combine the results obtained from multiple studies. Classical random-effects methods treat genetic heterogeneity as a random effect and consider it as a portion of the variance associated with a fixed effect of the variant. Recent work suggests performing hypothesis testing with the null hypothesis under which neither fixed nor random effects exist for a variant. This method has been shown to perform better than classical random-effects methods. In this work, we propose a meta-analysis of testing single nucleotide polymorphism (SNP)-environment interaction in the presence of genetic heterogeneity. We introduced the random effects of the SNP and SNP-environment interaction under test into a meta-regression model to account for heterogeneity. A test for the SNP-environment interaction was formulated to test for fixed and random effects of the interaction simultaneously. Similarly, a test for total genetic effects was formulated to test for fixed effects of the SNP and the SNP-environment interaction together with their random effects. We performed simulations to study the null distribution and statistical power of the proposed tests. We show that the new methods have higher power than classical random-effects and fixed-effects meta-regression methods when heterogeneity effects are large.
Hum Hered 2019;84:117–126


中文翻译:

具有异质性的SNP-环境相互作用的Meta分析

荟萃分析广泛用于全基因组关联研究中,以结合从多项研究中获得的结果。经典的随机效应方法将遗传异质性视为随机效应,并将其视为与变体的固定效应相关的方差的一部分。最近的工作建议使用无效假设执行假设检验,在该假设下,变量的固定效应和随机效应都不存在。与经典的随机效应方法相比,该方法的性能更好。在这项工作中,我们提出了在存在遗传异质性的情况下测试单核苷酸多态性(SNP)-环境相互作用的荟萃分析。我们将被测SNP和SNP与环境相互作用的随机效应引入到元回归模型中以说明异质性。制定了SNP与环境相互作用的测试,以同时测试相互作用的固定和随机作用。同样,制定了总遗传效应测试,以测试SNP和SNP与环境相互作用的固定效应以及它们的随机效应。我们进行了仿真,以研究拟议测试的零分布和统计功效。我们表明,当异质性影响较大时,新方法比经典随机效应和固定效应元回归方法具有更高的功效。我们进行了仿真,以研究拟议测试的零分布和统计功效。我们表明,当异质性影响较大时,新方法比经典随机效应和固定效应元回归方法具有更高的功效。我们进行了仿真,以研究拟议测试的零分布和统计功效。我们表明,当异质性影响较大时,新方法比经典随机效应和固定效应元回归方法具有更高的功效。
嗡嗡声到来的2019; 84:117–126
更新日期:2019-12-19
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