A CELLULAR AUTOMATA APPROACH TO DETECTING INTERACTIONS AMONG SINGLE-NUCLEOTIDE POLYMORPHISMS IN COMPLEX MULTIFACTORIAL DISEASES

摘要

The identification and characterization of susceptibility genes for common complex multifactorial human diseases remains a statistical and computational challenge. Parametric statistical methods such as logistic regression are limited in their ability to identify genes whose effects are dependent solely or partially on interactions with other genes and environmental exposures. We introduce cellular automata (CA) as a novel computational approach for identifying combinations of single-nucleotide polymorphisms (SNPs) associated with clinical endpoints. This alternative approach is nonparametric (i.e. no hypothesis about the value of a statistical parameter is made), is model-free (i.e. assumes no particular inheritance model), and is directly applicable to case-control and discordant sib-pair study designs. We demonstrate using simulated data that the approach has good power for identifying high-order nonlinear interactions (i.e. epistasis) among four SNPs in the absence of independent main effects.