title: SNP interaction pattern identifier (SIPI): an intensive search for SNP-SNP interaction patterns.
abstract: Testing SNP-SNP interactions is considered as a key for overcoming bottlenecks of genetic association studies. However, related statistical methods for testing SNP-SNP interactions are underdeveloped.
  
  
  
  We propose the SNP Interaction Pattern Identifier (SIPI), which tests 45 biologically meaningful interaction patterns for a binary outcome. SIPI takes non-hierarchical models, inheritance modes and mode coding direction into consideration. The simulation results show that SIPI has higher power than MDR (Multifactor Dimensionality Reduction), AA_Full, Geno_Full (full interaction model with additive or genotypic mode) and SNPassoc in detecting interactions. Applying SIPI to the prostate cancer PRACTICAL consortium data with approximately 21 000 patients, the four SNP pairs in EGFR-EGFR , EGFR-MMP16 and EGFR-CSF1 were found to be associated with prostate cancer aggressiveness with the exact or similar pattern in the discovery and validation sets. A similar match for external validation of SNP-SNP interaction studies is suggested. We demonstrated that SIPI not only searches for more meaningful interaction patterns but can also overcome the unstable nature of interaction patterns.
  
  
  
  The SIPI software is freely available at http://publichealth.lsuhsc.edu/LinSoftware/ .
  
  
  
  hlin1@lsuhsc.edu.
  
  
  
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, USA.
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mesh_terms: D004843:Epistasis, Genetic; D066246:ErbB Receptors / Q000235:genetics; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053513:Matrix Metalloproteinase 16 / Q000235:genetics; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012984:Software; D013223:Statistics as Topic
chemical_list: C507102:MMP16 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D053513:Matrix Metalloproteinase 16