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Abstract:
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Drug Induced Liver Injury (DILI) is the major cause of drug development failure or drug withdrawal from the market after development. The US government puts a lot of funds into investigating major causes and remedies of DILI. Therefore, investigating factors associated with DILI is of paramount importance. Environmental factors that contribute to DILI have been investigated and are, by and large, known. However, recent genomic studies have indicated that genetic diversity can lead to inter-individual differences in drug response. Consequently, it has become necessary to also investigate how genes contribute to DILI in the presence of environmental factors. Thus, our aim is to find appropriate statistical methods to investigate gene-gene and/or gene-environment interactions that are associated with DILI. This is an initial study that only explores statistical learning methods to find gen-gene interactions (epistasis). We introduce Multifactor Dimensionality Reduction (MDR), Random Forest (plus logistic regression), and Multivariate Adaptive Regression Splines (MARS), as the few potential methodological approaches that we found.
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