A method for detecting epistasis in genome-wide studies using case-control multi-locus association analysis.
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.
Gayán
Javier
J
Neocodex, Avda, Charles Darwin 6, Acc, A, 41092 Sevilla, Spain. gayan@well.ox.ac.uk
González-Pérez
Antonio
A
Bermudo
Fernando
F
Sáez
María Eugenia
ME
Royo
Jose Luis
JL
Quintas
Antonio
A
Galan
Jose Jorge
JJ
Morón
Francisco Jesús
FJ
Ramirez-Lorca
Reposo
R
Real
Luis Miguel
LM
Ruiz
Agustín
A
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