title: A global test for gene-gene interactions based on random matrix theory.
abstract: Statistical interactions between markers of genetic variation, or gene-gene interactions, are believed to play an important role in the etiology of many multifactorial diseases and other complex phenotypes. Unfortunately, detecting gene-gene interactions is extremely challenging due to the large number of potential interactions and ambiguity regarding marker coding and interaction scale. For many data sets, there is insufficient statistical power to evaluate all candidate gene-gene interactions. In these cases, a global test for gene-gene interactions may be the best option. Global tests have much greater power relative to multiple individual interaction tests and can be used on subsets of the markers as an initial filter prior to testing for specific interactions. In this paper, we describe a novel global test for gene-gene interactions, the global epistasis test (GET), that is based on results from random matrix theory. As we show via simulation studies based on previously proposed models for common diseases including rheumatoid arthritis, type 2 diabetes, and breast cancer, our proposed GET method has superior performance characteristics relative to existing global gene-gene interaction tests. A glaucoma GWAS data set is used to demonstrate the practical utility of the GET method.
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Frost
authors.affiliation: Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Division of Informatics, Department of Biostatistics and Epidemiology, Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D003198:Computer Simulation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D005819:Genetic Markers
keywords: gene-gene interaction; global test; random matrix theory