BOOST: A fast approach to detecting gene-gene interactions in genome-wide case-control studies

Gene-gene interactions have long been recognized to be fundamentally important to understand genetic causes of complex disease traits. At present, identifying gene-gene interactions from genome-wide case-control studies is computationally and methodologically challenging. In this paper, we introduce a simple but powerful method, named `BOolean Operation based Screening and Testing'(BOOST). To discover unknown gene-gene interactions that underlie complex diseases, BOOST allows examining all pairwise interactions in genome-wide case-control studies in a remarkably fast manner. We have carried out interaction analyses on seven data sets from the Wellcome Trust Case Control Consortium (WTCCC). Each analysis took less than 60 hours on a standard 3.0 GHz desktop with 4G memory running Windows XP system. The interaction patterns identified from the type 1 diabetes data set display significant difference from those identified from the rheumatoid arthritis data set, while both data sets share a very similar hit region in the WTCCC report. BOOST has also identified many undiscovered interactions between genes in the major histocompatibility complex (MHC) region in the type 1 diabetes data set. In the coming era of large-scale interaction mapping in genome-wide case-control studies, our method can serve as a computationally and statistically useful tool.

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