Testing zero variance components is one of the most challenging problems in the context of linear mixed-effects (LME) models. The usual asymptotic chi-square distribution of the likelihood ratio and score statistics under this null hypothesis is incorrect because the null is on the boundary of the parameter space. During the last two decades many tests have been proposed to overcome this difficulty, but these tests cannot be easily applied for testing multiple variance components, especially for testing a subset of them. We instead introduce a simple test statistic based on the variance least square estimator of variance components. With this comes a permutation procedure to approximate its finite sample distribution. The proposed test covers testing multiple variance components and any subset of them in LME models. Interestingly, our method does not depend on the distribution of the random effects and errors except for their mean and variance. We show, via simulations, that the proposed test has good operating characteristics with respect to Type I error and power. We conclude with an application of our process using real data from a study of the association of hyperglycemia and relative hyperinsulinemia.

It is traditionally assumed that the random effects in mixed models follow a multivariate normal distribution, making likelihood-based inferences more feasible theoretically and computationally. However, this assumption does not necessarily hold in practice which may lead to biased and unreliable results. We introduce a novel diagnostic test based on the so-called gradient function proposed by Verbeke and Molenberghs (2013) to assess the random-effects distribution. We establish asymptotic properties of our test and show that, under a correctly specified model, the proposed test statistic converges to a weighted sum of independent chi-squared random variables each with one degree of freedom. The weights, which are eigenvalues of a square matrix, can be easily calculated. We also develop a parametric bootstrap algorithm for small samples. Our strategy can be used to check the adequacy of any distribution for random effects in a wide class of mixed models, including linear mixed models, generalized linear mixed models, and non-linear mixed models, with univariate as well as multivariate random effects. Both asymptotic and bootstrap proposals are evaluated via simulations and a real data analysis of a randomized multicenter study on toenail dermatophyte onychomycosis.

High dimensional data are rapidly growing in many domains due to the development of technological advances which helps collect data with a large number of variables to better understand a given phenomenon of interest. Particular examples appear in genomics, fMRI data analysis, large-scale healthcare analytics, text/image analysis and astronomy. In the last two decades regularisation approaches have become the methods of choice for analysing such high dimensional data. This paper aims to study the performance of regularisation methods, including the recently proposed method called de-biased lasso, for the analysis of high dimensional data under different sparse and non-sparse situations. Our investigation concerns prediction, parameter estimation and variable selection. We particularly study the effects of correlated variables, covariate location and effect size which have not been well investigated. We find that correlated data when associated with important variables improve those common regularisation methods in all aspects, and that the level of sparsity can be reflected not only from the number of important variables but also from their overall effect size and locations. The latter may be seen under a non-sparse data structure. We demonstrate that the debiased lasso performs well especially in low dimensional data, however it still suffers from issues, such as multicollinearity and multiple hypothesis testing, similar to the classical regression methods.

In this paper, we develop a simple diagnostic test for the random-effects distribution in mixed models. The test is based on the gradient function, a graphical tool proposed by Verbeke and Molenberghs to check the impact of assumptions about the random-effects distribution in mixed models on inferences. Inference is conducted through the bootstrap. The proposed test is easy to implement and applicable in a general class of mixed models. The operating characteristics of the test are evaluated in a simulation study, and the method is further illustrated using two real data analyses.