Semiparametric analysis of case–control genetic data in the presence of environmental factors

In the past decade, many statistical methods have been proposed for the analysis of case-control genetic data with an emphasis on haplotype-based disease association studies. Most of the methodology has concentrated on the estimation of genetic (haplotype) main effects. Most methods accounted for environmental and gene-environment interaction effects by using prospective-type analyses that may lead to biased estimates when used with case-control data. Several recent publications addressed the issue of retrospective sampling in the analysis of case-control genetic data in the presence of environmental factors by developing efficient semiparametric statistical methods. This article describes the new Stata command haplologit, which implements efficient profile-likelihood semiparametric methods for fitting gene-environment models in the very important special cases of a rare disease, a single candidate gene in Hardy-Weinberg equilibrium, and independence of genetic and environmental factors. Copyright 2008 by StataCorp LP.