title: Identification of interactions using model-based multifactor dimensionality reduction.
abstract: BACKGROUND
  Common complex traits may involve multiple genetic and environmental factors and their interactions. Many methods have been proposed to identify these interaction effects, among them several machine learning and data mining methods. These are attractive for identifying interactions because they do not rely on specific genetic model assumptions. To handle the computational burden arising from an exhaustive search, including all possible combinations of factors, filter methods try to select promising factors in advance.
  
  
  METHODS
  Model-based multifactor dimensionality reduction (MB-MDR), a semiparametric machine learning method allowing adjustment for confounding variables and lower level effects, is applied to Genetic Analysis Workshop 19 (GAW19) data to identify interaction effects on different traits. Several filtering methods based on the nearest neighbor algorithm are assessed in terms of compatibility with MB-MDR.
  
  
  RESULTS
  Single nucleotide polymorphism (SNP) rs859400 shows a significant interaction effect (correctedpvalue <0.05) with age on systolic blood pressure (SBP). We identified 23 SNP-SNP interaction effects on hypertension status (HS), 42 interaction effects on SBP, and 26 interaction effects on diastolic blood pressure (DBP). Several of these SNPs are in strong linkage disequilibrium (LD). Three of the interaction effects on HS are identified in filtered subsets.
  
  
  CONCLUSIONS
  The considered filtering methods seem not to be appropriate to use with MB-MDR. LD pruning is further quality control to be incorporated, which can reduce the combinatorial burden by removing redundant SNPs.
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Ratzeburger Allee 160, Lübeck, 23562 Germany.
authors.forename: Damian
authors.initials: D
authors.lastname: Gola
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein - Campus Lübeck, Ratzeburger Allee 160, Lübeck, 23562 Germany.
authors.forename: Inke R
authors.initials: IR
authors.lastname: König