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Abstract #69288 Published in IGR 18-1
A global test for gene-gene interactions based on random matrix theory
Frost HR; Amos CI; Moore JHGenetic epidemiology 2016; 40: 689-701
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.
Department of Biomedical Data Science, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States of America.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)