Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests

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Many of our common diseases are driven by complex interactions between multiple genetic factors. Disease-specific, genome-wide association studies have been the prominent tool for cataloging such factors, by studying the genetic variation of a gene in a population and its association with the disease. However, these studies often fail to capture interactions between genes despite their importance. Interactions are notoriously difficult to investigate, because testing the large number of possible interactions using contemporary statistical methods requires very large sample sizes and computational resources. We have taken a step forward by developing a new statistical methodology that significantly reduces these requirements, making the study of interactions more feasible. We show that our methodology makes it possible to study interactions on a large scale without compromising the statistical accuracy. We further demonstrate the utility of our methodology on data relating to coronary artery disease and discover three distinct interactions that might provides new clues to the pathophysiology. The study of genetic interactions have the potential to link disease genes together into disease networks that provide a more detailed description of the interaction between genes and how it drives the disease.

Vyšlo v časopise: Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005502
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005502

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