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Bioinformatics Advance Access originally published online on November 8, 2006
Bioinformatics 2007 23(1):71-76; doi:10.1093/bioinformatics/btl557
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Odds ratio based multifactor-dimensionality reduction method for detecting gene–gene interactions

Yujin Chung 1, Seung Yeoun Lee 2, Robert C. Elston 3 and Taesung Park 1,*

1 Department of Statistics, Seoul National University San 56-1 Shillim-Dong, Kwanak-Gu, Seoul 151-747, Korea
2 Department of Applied Mathematics, Sejong University 98 Gunja-Dong Kwangjin-Gu, Seoul 143-747, Korea
3 Department of Epidemiology and Biostatistics, Case Western Reserve University 10900 Euclid Avenue Cleveland, OH 44106-7281, USA

*To whom correspondence should be addressed.

Motivation: The identification and characterization of genes that increase the susceptibility to common complex multifactorial diseases is a challenging task in genetic association studies. The multifactor dimensionality reduction (MDR) method has been proposed and implemented by Ritchie et al. (2001) to identify the combinations of multilocus genotypes and discrete environmental factors that are associated with a particular disease. However, the original MDR method classifies the combination of multilocus genotypes into high-risk and low-risk groups in an ad hoc manner based on a simple comparison of the ratios of the number of cases and controls. Hence, the MDR approach is prone to false positive and negative errors when the ratio of the number of cases and controls in a combination of genotypes is similar to that in the entire data, or when both the number of cases and controls is small. Hence, we propose the odds ratio based multifactor dimensionality reduction (OR MDR) method that uses the odds ratio as a new quantitative measure of disease risk.

Results: While the original MDR method provides a simple binary measure of risk, the OR MDR method provides not only the odds ratio as a quantitative measure of risk but also the ordering of the multilocus combinations from the highest risk to lowest risk groups. Furthermore, the OR MDR method provides a confidence interval for the odds ratio for each multilocus combination, which is extremely informative in judging its importance as a risk factor. The proposed OR MDR method is illustrated using the dataset obtained from the CDC Chronic Fatigue Syndrome Research Group.

Availability: The program written in R is available.

Contact: tspark{at}snu.ac.kr

Received on June 27, 2006; revised on September 11, 2006; accepted on October 27, 2006

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