title: Global adaptive rank truncated product method for gene-set analysis in association studies.
abstract: 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.
authors.affiliation: 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.|CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Vilor-Tejedor
authors.affiliation: Department of Systems Biology, Bioinformatics and Medical Statistics Group, Universitat de Vic - Universitat Central de Catalunya, C. Sagrada Familia, 7, 08570-Vic, Spain.
authors.forename: M Luz
authors.initials: ML
authors.lastname: Calle
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D016022:Case-Control Studies; D003198:Computer Simulation; D004705:Endocytosis; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: ARTP; Adaptive method; Alzheimer's disease; Endocytosis pathway; Gene set analysis; Genetic susceptibility; GlobalARTP; Single-SNP analysis