title: A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis.
abstract: BACKGROUND
  The difficulty in elucidating the genetic basis of complex diseases roots in the many factors that can affect the development of a disease. Some of these genetic effects may interact in complex ways, proving undetectable by current single-locus methodology.
  
  
  RESULTS
  We have developed an analysis tool called Hypothesis Free Clinical Cloning (HFCC) to search for genome-wide epistasis in a case-control design. HFCC combines a relatively fast computing algorithm for genome-wide epistasis detection, with the flexibility to test a variety of different epistatic models in multi-locus combinations. HFCC has good power to detect multi-locus interactions simulated under a variety of genetic models and noise conditions. Most importantly, HFCC can accomplish exhaustive genome-wide epistasis search with large datasets as demonstrated with a 400,000 SNP set typed on a cohort of Parkinson's disease patients and controls.
  
  
  CONCLUSIONS
  With the current availability of genetic studies with large numbers of individuals and genetic markers, HFCC can have a great impact in the identification of epistatic effects that escape the standard single-locus association analyses.
authors.affiliation: Neocodex, Avda, Charles Darwin 6, Acc, A, 41092 Sevilla, Spain. gayan@well.ox.ac.uk
authors.forename: Javier
authors.initials: J
authors.lastname: Gayán
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermudo
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Sáez
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Royo
authors.forename: Antonio
authors.initials: A
authors.lastname: Quintas
authors.forename: Jose Jorge
authors.initials: JJ
authors.lastname: Galan
authors.forename: Francisco Jesús
authors.initials: FJ
authors.lastname: Morón
authors.forename: Reposo
authors.initials: R
authors.lastname: Ramirez-Lorca
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Real
authors.forename: Agustín
authors.initials: A
authors.lastname: Ruiz
mesh_terms: D000465:Algorithms; D016022:Case-Control Studies; D015331:Cohort Studies; D030541:Databases, Genetic; D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease; D005821:Genetic Techniques / Q000706:statistics & numerical data; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D015999:Multivariate Analysis; D010300:Parkinson Disease / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012984:Software