Abstract

Combinatorial pharmacogenetics seeks to characterize genetic variations that affect reactions to potentially toxic agents within the complex metabolic networks of the human body. Polymorphic drug-metabolizing enzymes are likely to represent some of the most common inheritable risk factors associated with common 'disease' phenotypes, such as adverse drug reactions. The relatively high concordance between polymorphisms in drug-metabolizing enzymes and clinical phenotypes indicates that research into this class of polymorphisms could benefit patients in the near future. Characterization of other genes affecting drug disposition (absorption, distribution, metabolism and elimination) will further enhance this process. As with most questions concerning biological systems, the complexity arises out of the combinatorial magnitude of all the possible interactions and pathways. The high-dimensionality of the resulting analysis problem will often overwhelm traditional analysis methods. Novel analysis techniques, such as multifactor dimensionality reduction, offer viable options for evaluating such data.

Author affiliations

1. Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA.
2. Computational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, New Hampshire, USA.
3. Computational Genetics Laboratory, Norris-Cotton Cancer Center, Departments of Genetics, and Community and Family Medicine, Dartmouth Medical School, Lebanon; Department of Biological Sciences, Dartmouth College, Hanover; Department of Computer Science, University of New Hampshire, New Hampshire; 706 Rubin, HB7937, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, New Hampshire 03756, USA.

Correspondence to: Jason H. Moore³ Email: jason.h.moore@dartmouth.edu

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