INTRAPID: A tool for genome wide analysis of interaction between SNPs.

Background:

Genome-wide association studies (GWAS) have established themselves as the most successful approach to mapping the genetic determinants of complex human traits. However, so far most of the large studies have focussed on tracking for marginal effects only. This has resulted in explanation of only a small percentage of the genetic component of phenotypic variation. There is plenty of evidence from model organisms to show that complex traits could be influenced by interaction between genes, where the function of one gene could be influenced by the presence of another remote gene. An exhautive scan for interactive effects in a genome seems essential to better understand the genetic architecture of complex diseases. One problem though is the computational burden that comes with it, for most modern day GWAS sample sizes. Given, its lack of feasibility at the moment, such studies have hardly been conducted.

INTRAPID is able to conduct such studies very efficiently, by reducing the analysis time by more than 95%. Rather than using a traditional regression method, it uses a two stage method, where stage one uses a rapid interaction method. For a binary trait, this is equivalent to the "fast-epistasis" method, described in PLINK. Continuous traits are dichotomised at the median, creating pseudo-cases and pseudo-controls. Simulation studies show that this does not result in any significant loss in power.