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Int. J. Mol. Sci. 2014, 15(6), 10724-10737; doi:10.3390/ijms150610724
Article

Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma

1,2,3
, 1,* , 2
 and 2,*
Received: 4 March 2014; in revised form: 21 April 2014 / Accepted: 3 June 2014 / Published: 13 June 2014
(This article belongs to the collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Abstract: Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.
Keywords: gene-gene interaction; weighted risk score; multifactor dimensionality reduction; nasopharyngeal carcinoma gene-gene interaction; weighted risk score; multifactor dimensionality reduction; nasopharyngeal carcinoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Li, C.-F.; Luo, F.-T.; Zeng, Y.-X.; Jia, W.-H. Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma. Int. J. Mol. Sci. 2014, 15, 10724-10737.

AMA Style

Li C-F, Luo F-T, Zeng Y-X, Jia W-H. Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma. International Journal of Molecular Sciences. 2014; 15(6):10724-10737.

Chicago/Turabian Style

Li, Chao-Feng; Luo, Fu-Tian; Zeng, Yi-Xin; Jia, Wei-Hua. 2014. "Weighted Risk Score-Based Multifactor Dimensionality Reduction to Detect Gene-Gene Interactions in Nasopharyngeal Carcinoma." Int. J. Mol. Sci. 15, no. 6: 10724-10737.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert