- Article -
| In Silico Biology 4, 0016 (2004); ©2004, Bioinformation Systems e.V. |
Ideal discrimination of discrete clinical endpoints using multilocus genotypes
Lance W. Hahn and Jason H. Moore*
Center for Human Genetics Research, 519 Light Hall, Vanderbilt University, Nashville, TN 37232-0700, USA
Email: moore@chgr.mc.vanderbilt.edu
* corresponding author
Edited by H. Michael and E. Wingender; received August 08, 2003; revised February 02; accepted February 06, 2004; published February 11, 2004
Abstract
Multifactor Dimensionality Reduction (MDR) is a method for the classification and prediction of discrete clinical endpoints using attributes constructed from multilocus genotype data. Empirical studies with both real and simulated data suggest that MDR has good power for detecting gene-gene interactions in the absence of independent main effects. The purpose of this study is to develop an objective, theory-driven approach to evaluate the strengths and limitations of MDR. To accomplish this goal, we borrow concepts from ideal observer analysis used in visual perception to evaluate the theoretical limits of classifying and predicting discrete clinical endpoints using multilocus genotype data. We conclude that MDR ideally discriminates between low risk and high risk subjects using attributes constructed from multilocus genotype data. We also how that the classification approach used once a multilocus attribute is constructed is similar to that of a naïve Bayes classifier. This study provides a theoretical foundation for the continued development, evaluation, and application of the MDR as a data mining tool in the domain of statistical genetics and genetic epidemiology.
Key words: multifactor dimensionality reduction, epistasis, gene-gene interaction, ideal observer, naÏve Bayes classifier