Power of Competing Strategies of Linkage Analysis for Complex Traits

Abstract

Variance components (VC) and the Bayesian Markov chain Monte Carlo (MCMC) analysis are two of the widely used linkage analysis approaches to mapping genes for complex quantitative traits. Both approaches can handle extended pedigrees and multiple markers and do not require a prespecified genetic model. In this study, we used simulated data to compare the performance of these two approaches with the traditional parametric linkage analysis. Using simulated data sets without linkage between a quantitative trait and the markers, we estimated a critical value for various test scores used in VC or MCMC and the location (LOC) score at a fixed level of significance (5%). These critical values were then used to determine the power for the three methods for simulated data sets with linkage. We found that both the VC and MCMC approaches worked well, compared with the LOC score, when there was only one gene underlying the quantitative trait; however, VC had higher power than the other methods in a simulation study of a complex phenotype influenced by more than one gene. We also compared two implementations of MCMC analysis, finding interpretation of results using the log of placement score was more accurate for linkage inference than the Bayes factor but required much more intensive simulation studies.