title: GWGGI: software for genome-wide gene-gene interaction analysis.
abstract: BACKGROUND
  While the importance of gene-gene interactions in human diseases has been well recognized, identifying them has been a great challenge, especially through association studies with millions of genetic markers and thousands of individuals. Computationally efficient and powerful tools are in great need for the identification of new gene-gene interactions in high-dimensional association studies.
  
  
  RESULTS
  We develop C++ software for genome-wide gene-gene interaction analyses (GWGGI). GWGGI utilizes tree-based algorithms to search a large number of genetic markers for a disease-associated joint association with the consideration of high-order interactions, and then uses non-parametric statistics to test the joint association. The package includes two functions, likelihood ratio Mann-Whitney (LRMW) and Tree Assembling Mann-Whitney (TAMW). We optimize the data storage and computational efficiency of the software, making it feasible to run the genome-wide analysis on a personal computer. The use of GWGGI was demonstrated by using two real data-sets with nearly 500 k genetic markers.
  
  
  CONCLUSIONS
  Through the empirical study, we demonstrated that the genome-wide gene-gene interaction analysis using GWGGI could be accomplished within a reasonable time on a personal computer (i.e., ~3.5 hours for LRMW and ~10 hours for TAMW). We also showed that LRMW was suitable to detect interaction among a small number of genetic variants with moderate-to-strong marginal effect, while TAMW was useful to detect interaction among a larger number of low-marginal-effect genetic variants.
authors.forename: Changshuai
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Epidemiology and Biostatistics, Michigan State University, East Lansing 48824, MI, USA. qlu@epi.msu.edu.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011381:Programming Languages; D012984:Software