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Addressing the Challenges of Detecting Epistasis in Genome-Wide Association Studies of Common Human Diseases Using Biological Expert Knowledge
Abstract
Recent technological developments in the field of genetics have given rise to an abundance of research tools, such as genome-wide genotyping, that allow researchers to conduct genome-wide association studies (GWAS) for detecting genetic variants that confer increased or decreased susceptibility to disease. However, discovering epistatic, or gene-gene, interactions in high dimensional datasets is a problem due to the computational complexity that results from the analysis of all possible combinations of single-nucleotide polymorphisms (SNPs). A recently explored approach to this problem employs biological expert knowledge, such as pathway or protein-protein interaction information, to guide an analysis by the selection or weighting of SNPs based on this knowledge. Narrowing the evaluation to gene combinations that have been shown to interact experimentally provides a biologically concise reason why those two genes may be detected together statistically. This chapter discusses the challenges of discovering epistatic interactions in GWAS and how biological expert knowledge can be used to facilitate genome-wide genetic studies.
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