Detecting gene-gene interactions using affected sib pair analysis with covariates.

Abstract

Interest has recently focussed on allowing for interactions between loci as a way to increase power to detect linkage. In this paper, a simplified logistic regression method was used to perform affected sib pair analyses allowing for the inclusion of data from other loci. A systematic search of two-locus disease models was carried out to determine the situations in which this was advantageous. If IBD information is available (e.g. from a genome scan), it is unlikely that allowing for interactions will give a large lod score in the absence of linkage evidence from sinlge-locus analysis. Furthermore, allowing for interactions rarely gave a significant increase in power to detect linkage over a single-locus analysis, except for heterogeneity models with low K(P). Conversely, the availability of disease-associated genotypes may greatly increase the power both to detect linkage to a second locus and interaction between the loci. These results indicate that when only IBD information is available, two-locus analysis of genome scan data should be restricted to regions giving peaks under single-locus analysis. If disease-associated genotypes are available, it may be worth re-analysing the whole genome.