Vilor-Tejedor Natalia, Calle M Luz
Centre for Research in Environmental Epidemiology (CREAL), C. Doctor Aiguader, 88, 08003-Barcelona, Spain.
Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain.
Biom J. 2014 Sep;56(5):901-11. doi: 10.1002/bimj.201300192. Epub 2014 Aug 1.
Gene set analysis (GSA) aims to assess the overall association of a set of genetic variants with a phenotype and has the potential to detect subtle effects of variants in a gene or a pathway that might be missed when assessed individually. We present a new implementation of the Adaptive Rank Truncated Product method (ARTP) for analyzing the association of a set of Single Nucleotide Polymorphisms (SNPs) in a gene or pathway. The new implementation, referred to as globalARTP, improves the original one by allowing the different SNPs in the set to have different modes of inheritance. We perform a simulation study for exploring the power of the proposed methodology in a set of scenarios with different numbers of causal SNPs with different effect sizes. Moreover, we show the advantage of using the gene set approach in the context of an Alzheimer's disease case-control study where we explore the endocytosis pathway. The new method is implemented in the R function globalARTP of the globalGSA package available at http://cran.r-project.org.
基因集分析（GSA）旨在评估一组基因变异与一种表型之间的总体关联，并且有潜力检测单个评估时可能会遗漏的基因或通路中变异的细微效应。我们提出了一种用于分析基因或通路中一组单核苷酸多态性（SNP）关联的自适应秩截断乘积方法（ARTP）的新实现方式。这种新实现方式被称为全局ARTP，它通过允许集合中的不同SNP具有不同的遗传模式改进了原始方法。我们进行了一项模拟研究，以探索在具有不同数量、不同效应大小的因果SNP的一组场景中所提出方法的效能。此外，我们展示了在阿尔茨海默病病例对照研究背景下使用基因集方法的优势，在此研究中我们探索了内吞作用通路。新方法在可从http://cran.r-project.org获取的全局GSA包的R函数globalARTP中实现。
