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BMC Bioinformatics. 2006 Jan 25;7:39.

GPNN: power studies and applications of a neural network method for detecting gene-gene interactions in studies of human disease.

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Center for Human Genetics Research, Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0700, USA.



The identification and characterization of genes that influence the risk of common, complex multifactorial disease primarily through interactions with other genes and environmental factors remains a statistical and computational challenge in genetic epidemiology. We have previously introduced a genetic programming optimized neural network (GPNN) as a method for optimizing the architecture of a neural network to improve the identification of gene combinations associated with disease risk. The goal of this study was to evaluate the power of GPNN for identifying high-order gene-gene interactions. We were also interested in applying GPNN to a real data analysis in Parkinson's disease.


We show that GPNN has high power to detect even relatively small genetic effects (2-3% heritability) in simulated data models involving two and three locus interactions. The limits of detection were reached under conditions with very small heritability (<1%) or when interactions involved more than three loci. We tested GPNN on a real dataset comprised of Parkinson's disease cases and controls and found a two locus interaction between the DLST gene and sex.


These results indicate that GPNN may be a useful pattern recognition approach for detecting gene-gene and gene-environment interactions.

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