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

Alison A. Motsinger, Stephen L. Lee, George Mellick, Marylyn D. Ritchie

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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

Original languageEnglish (US)
Article number39
JournalBMC bioinformatics
Volume7
DOIs
StatePublished - Jan 25 2006

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics

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