title: Filter-free exhaustive odds ratio-based genome-wide interaction approach pinpoints evidence for interaction in the HLA region in psoriasis.
abstract: BACKGROUND
  Deciphering the genetic architecture of complex traits is still a major challenge for human genetics. In most cases, genome-wide association studies have only partially explained the heritability of traits and diseases. Epistasis, one potentially important cause of this missing heritability, is difficult to explore at the genome-wide level. Here, we develop and assess a tool based on interactive odds ratios (IOR), Fast Odds Ratio-based sCan for Epistasis (FORCE), as a novel approach for exhaustive genome-wide epistasis search. IOR is the ratio between the multiplicative term of the odds ratio (OR) of having each variant over the OR of having both of them. By definition, an IOR that significantly deviates from 1 suggests the occurrence of an interaction (epistasis). As the IOR is fast to calculate, we used the IOR to rank and select pairs of interacting polymorphisms for P value estimation, which is more time consuming.
  
  
  RESULTS
  FORCE displayed power and accuracy similar to existing parametric and non-parametric methods, and is fast enough to complete a filter-free genome-wide epistasis search in a few days on a standard computer. Analysis of psoriasis data uncovered novel epistatic interactions in the HLA region, corroborating the known major and complex role of the HLA region in psoriasis susceptibility.
  
  
  CONCLUSIONS
  Our systematic study revealed the ability of FORCE to uncover novel interactions, highlighted the importance of exhaustiveness, as well as its specificity for certain types of interactions that were not detected by existing approaches. We therefore believe that FORCE is a valuable new tool for decoding the genetic basis of complex diseases.
authors: Department of Genomes and Genetics, Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, 75015, France. laura.bea.grange@gmail.com.|CNRS URA3012, Paris, 75015, France. laura.bea.grange@gmail.com.|Université Paris Diderot, Paris, 75013, France. laura.bea.grange@gmail.com.
authors: Laura
authors: L
authors: Grange
authors: Department of Genomes and Genetics, Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, 75015, France. jfb@pasteur.fr.|CNRS URA3012, Paris, 75015, France. jfb@pasteur.fr.
authors: Jean-François
authors: JF
authors: Bureau
authors: Department of Genomes and Genetics, Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, 75015, France. iryna.nikolayeva@pasteur.fr.|Department of Genomes and Genetics, Institut Pasteur, Systems Biology Lab, Paris, 75015, France. iryna.nikolayeva@pasteur.fr.|Université Paris-Descartes, Sorbonne Paris Cité, Paris, France. iryna.nikolayeva@pasteur.fr.
authors: Iryna
authors: I
authors: Nikolayeva
authors: Department of Genomes and Genetics, Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, 75015, France. richard.paul@pasteur.fr.|CNRS URA3012, Paris, 75015, France. richard.paul@pasteur.fr.
authors: Richard
authors: R
authors: Paul
authors: Systems and Modeling Unit, Montefiore institute, University of Liège, Liège, Belgium. kristel.vansteen@ulg.ac.be.|Bioinformatics and Modeling, GiGA-R, University of Liège, Liège, Belgium. kristel.vansteen@ulg.ac.be.
authors: Kristel
authors: K
authors: Van Steen
authors: Department of Genomes and Genetics, Institut Pasteur, Systems Biology Lab, Paris, 75015, France. benno@pasteur.fr.
authors: Benno
authors: B
authors: Schwikowski
authors: Department of Genomes and Genetics, Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Paris, 75015, France. anavaj@pasteur.fr.|CNRS URA3012, Paris, 75015, France. anavaj@pasteur.fr.
authors: Anavaj
authors: A
authors: Sakuntabhai
mesh_terms: D002896:Chromosomes, Human, Pair 6; D004843:Epistasis, Genetic; D055106:Genome-Wide Association Study / Q000379:methods*; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics*; D012984:Software
chemical_list: D006649:Histocompatibility Antigens
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