A generalized,multi-stage adjusted,latent class linear mixed model for testing genetic association

ABSTRACT

In this study, a Generalized, Multi-Stage Adjusted, Latent Class Linear Mixed Model is proposed for modeling the heterogeneous distributed phenotype and genetic information across the whole genome in the presence of both serial and familial correlations. Genome data were analyzed by applying the proposed model to Genetic Analysis Workshop (GAW) data, and the model results were compared to the results of standard models. Moreover, the potential of the model is discussed compared to simulated data. As a result of model comparisons, the information criteria and the genomic control parameter were found to be smaller. The results of a power analysis show that the proposed model is more powerful.     

Empirical Uncertain Bayes Methods in Area‐level Models

Random effects model can account for the lack of fitting a regression model and increase precision of estimating area‐level means. However, in case that the synthetic mean provides accurate estimates, the prior distribution may inflate an estimation error. Thus, it is desirable to consider the uncertain prior distribution, which is expressed as the mixture of a one‐point distribution and a proper prior distribution. In this paper, we develop an empirical Bayes approach for estimating area‐level means, using the uncertain prior distribution in the context of a natural exponential family, which we call the empirical uncertain Bayes (EUB) method. The regression model considered in this paper includes the Poisson‐gamma and the binomial‐beta, and the normal‐normal (Fay–Herriot) model, which are typically used in small area estimation. We obtain the estimators of hyperparameters based on the marginal likelihood by using a well‐known expectation‐maximization algorithm and propose the EUB estimators of area means. For risk evaluation of the EUB estimator, we derive a second‐order unbiased estimator of a conditional mean squared error by using some techniques of numerical calculation. Through simulation studies and real data applications, we evaluate a performance of the EUB estimator and compare it with the usual empirical Bayes estimator.