The null distribution of likelihood-ratio statistics in the conditional-logistic linkage model

Abstract

Olson's conditional-logistic model retains the nice property of the LOD score formulation and has advantages over other methods that make it an appropriate choice for complex trait linkage mapping. However, the asymptotic distribution of the conditional-logistic likelihood-ratio (CL-LR) statistic with genetic constraints on the model parameters is unknown for some analysis models, even in the case of samples comprising only independent sib pairs. We derive approximations to the asymptotic null distributions of the CL-LR statistics and compare them with the empirical null distributions by simulation using independent affected sib pairs. Generally, the empirical null distributions of the CL-LR statistics match well the known or approximated asymptotic distributions for all analysis models considered except for the covariate model with a minimum-adjusted binary covariate. This work will provide useful guidelines for linkage analysis of real data sets for the genetic analysis of complex traits, thereby contributing to the identification of genes for disease traits.

Novel Approaches to the Analysis of Family Data in Genetic Epidemiology

“…This method, which uniquely combines MCMC based approximations with non-stochastic approaches, can be used to map disease genes using linkage and/or association evidence. Song and Elston (2013a) investigate the distributional properties of a commonly used linkage analysis statistic. These authors also describe a new web based software package which, among other things, plots pedigrees, calculates genetic similarity coefficients and performs visualization of the relatedness among family members (Song and Elston, 2013b).…”

Novel approaches to the analysis of family data in genetic epidemiology

“…This method, which uniquely combines MCMC based approximations with non-stochastic approaches, can be used to map disease genes using linkage and/or association evidence. Song and Elston ( 2013a ) investigate the distributional properties of a commonly used linkage analysis statistic. These authors also describe a new web based software package which, among other things, plots pedigrees, calculates genetic similarity coefficients and performs visualization of the relatedness among family members (Song and Elston, 2013b ).…”