Cox proportional hazards survival regression in haplotype-based association analysis using the Stochastic-EM algorithm.

It is now widely recognized that haplotype information inferred from genotypes can be of great interest to better characterize the role of a candidate gene in the etiology of a complex trait in the context of association studies. Several works have recently advocated the simultaneous estimation of haplotype frequencies and haplotype effects in order to get a better efficiency in parameter estimation. Most of the available models can deal with a binary or a quantitative phenotype, but none has yet discussed the application of haplotype-based association analysis to a survival outcome. We describe how the recently proposed Stochastic-EM (SEM) algorithm can be applied to estimate haplotype effects in censored data analysis using a standard Cox proportional hazards formulation. This model has been implemented in the THESIAS software freely available at http://www.genecanvas.org.