CGene: An R package for implementation of causal genetic analyses

Abstract

The excitement over findings from Genome-Wide Association Studies (GWASs) has been tempered by the difficulty in finding the location of the true causal disease susceptibility loci (DSLs), rather than markers that are correlated with the causal variants. In addition, many recent GWASs have studied multiple phenotypes - often highly correlated - making it difficult to understand which associations are causal and which are seemingly causal, induced by phenotypic correlations. In order to identify DSLs, which are required to understand the genetic etiology of the observed associations, statistical methodology has been proposed that distinguishes between a direct effect of a genetic locus on the primary phenotype and an indirect effect induced by the association with the intermediate phenotype that is also correlated with the primary phenotype. However, so far, the application of this important methodology has been challenging, as no user-friendly software implementation exists. The lack of software implementation of this sophisticated methodology has prevented its large-scale use in the genetic community. We have now implemented this statistical approach in a user-friendly and robust R package that has been thoroughly tested. The R package CGene is available for download at http://cran.r-project.org/. The R code is also available at http://people.hsph. harvard.edu/∼plipman. © 2011 Macmillan Publishers Limited All rights.