title: Identifying genetic interactions associated with late-onset Alzheimer's disease.
abstract: BACKGROUND
  Identifying genetic interactions in data obtained from genome-wide association studies (GWASs) can help in understanding the genetic basis of complex diseases. The large number of single nucleotide polymorphisms (SNPs) in GWASs however makes the identification of genetic interactions computationally challenging. We developed the Bayesian Combinatorial Method (BCM) that can identify pairs of SNPs that in combination have high statistical association with disease.
  
  
  RESULTS
  We applied BCM to two late-onset Alzheimer's disease (LOAD) GWAS datasets to identify SNPs that interact with known Alzheimer associated SNPs. We also compared BCM with logistic regression that is implemented in PLINK. Gene Ontology analysis of genes from the top 200 dataset SNPs for both GWAS datasets showed overrepresentation of LOAD-related terms. Four genes were common to both datasets: APOE and APOC1, which have well established associations with LOAD, and CAMK1D and FBXL13, not previously linked to LOAD but having evidence of involvement in LOAD. Supporting evidence was also found for additional genes from the top 30 dataset SNPs.
  
  
  CONCLUSIONS
  BCM performed well in identifying several SNPs having evidence of involvement in the pathogenesis of LOAD that would not have been identified by univariate analysis due to small main effect. These results provide support for applying BCM to identify potential genetic variants such as SNPs from high dimensional GWAS datasets.
authors: Department of Biomedical Informatics, University of Pittsburgh, 5607 Baum Boulevard, Pittsburgh, PA 15206 USA.
authors: Charalampos S
authors: CS
authors: Floudas
authors: Department of Biomedical Informatics, University of Pittsburgh, 5607 Baum Boulevard, Pittsburgh, PA 15206 USA.
authors: Nara
authors: N
authors: Um
authors: Department of Human Genetics, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261 USA.
authors: M Ilyas
authors: MI
authors: Kamboh
authors: Department of Human Genetics, University of Pittsburgh, 130 De Soto Street, Pittsburgh, PA 15261 USA.
authors: Michael M
authors: MM
authors: Barmada
authors: Department of Biomedical Informatics, University of Pittsburgh, 5607 Baum Boulevard, Pittsburgh, PA 15206 USA ; The Intelligent Systems Program, University of Pittsburgh, 5113 Sennott Square 210 South Bouquet Street, Pittsburgh, PA 15260 USA.
authors: Shyam
authors: S
authors: Visweswaran
keywords: Alzheimer’s disease; Bayesian networks; Epistasis; Genome-wide association study
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