Case–control genome-wide joint association study using semiparametric empirical model and approximate Bayes factor

We propose a semiparametric approach for the analysis of case–control genome-wide association study. Parametric components are used to model both the conditional distribution of the case status given the covariates and the distribution of genotype counts, whereas the distribution of the covariates are modelled nonparametrically. This yields a direct and joint modelling of the case status, covariates and genotype counts, and gives a better understanding of the disease mechanism and results in more reliable conclusions. Side information, such as the disease prevalence, can be conveniently incorporated into the model by an empirical likelihood approach and leads to more efficient estimates and a powerful test in the detection of disease-associated SNPs. Profiling is used to eliminate a nuisance nonparametric component, and the resulting profile empirical likelihood estimates are shown to be consistent and asymptotically normal. For the hypothesis test on disease association, we apply the approximate Bayes factor (ABF) which is computationally simple and most desirable in genome-wide association studies where hundreds of thousands to a million genetic markers are tested. We treat the approximate Bayes factor as a hybrid Bayes factor which replaces the full data by the maximum likelihood estimates of the parameters of interest in the full model and derive it under a general setting. The deviation from Hardy–Weinberg Equilibrium (HWE) is also taken into account and the ABF for HWE using cases is shown to provide evidence of association between a disease and a genetic marker. Simulation studies and an application are further provided to illustrate the utility of the proposed methodology.     

An Adaptive Test for the Two-Sample Location Problem Based on U-Statistics

For the two-sample location problem with continuous data we consider a general class of tests, all members of it are based on U-statistics. The asymptotic efficacies are investigated in detail. We construct an adaptive test where all statistics involved are suitably chosen U-statistics. It is shown that the proposed adaptive test has good asymptotic and finite sample power properties.     

Use of several auxiliary variables in estimating the population mean in a two-occasion rotation pattern

ABSTRACT

This paper addresses the problem of estimation of the population mean on the current (second) occasion in two-occasion successive sampling. Utilizing the readily available information on several auxiliary variables on both occasions and the information on the study variable from the previous occasion, an estimation procedure of the population mean on the current occasion has been proposed. Theoretical properties of the proposed estimator have been investigated. Optimum replacement policy to the proposed estimator has been discussed. The proposed estimator has been compared empirically with the sample mean estimator, when there is no matching and the optimum estimator which is a linear combination of the means of the matched and unmatched portions of the sample at the current occasion. Appropriate recommendations have been made for practical applications.     

Comparing a New Gini Test with Other Symmetry Tests When Median Is Unknown

Although there exists an ample literature on the tests of univariate symmetry, each article provides comparison of few selected competitors only. We are comparing the performance of 15 tests recommended in the literature and two new methods introduced by Auda (2006 Auda (Ouda), H. 2006. New Tests of Univariate Symmetry Based on the Gini Mean Difference, Kalamazoo, MI: Western Michigan University. Ph.D. thesis [Google Scholar]). One of them, rank-based test RS, compares favorably with several existing procedures in controlling the Type I error as well as in power as shown in our comprehensive simulation study. An important novelty in the article are Figs. 1– 3 enabling comparison of Type I error probabilities and power of the 16 tests for 17 null and 19 alternative distributions.     

Sample Size Calculation and Blinded Sample Size Recalculation in Clinical Trials Where the Treatment Effect is Measured by the Relative Risk

In clinical trials with binary endpoints, the required sample size does not depend only on the specified type I error rate, the desired power and the treatment effect but also on the overall event rate which, however, is usually uncertain. The internal pilot study design has been proposed to overcome this difficulty. Here, nuisance parameters required for sample size calculation are re-estimated during the ongoing trial and the sample size is recalculated accordingly. We performed extensive simulation studies to investigate the characteristics of the internal pilot study design for two-group superiority trials where the treatment effect is captured by the relative risk. As the performance of the sample size recalculation procedure crucially depends on the accuracy of the applied sample size formula, we firstly explored the precision of three approximate sample size formulae proposed in the literature for this situation. It turned out that the unequal variance asymptotic normal formula outperforms the other two, especially in case of unbalanced sample size allocation. Using this formula for sample size recalculation in the internal pilot study design assures that the desired power is achieved even if the overall rate is mis-specified in the planning phase. The maximum inflation of the type I error rate observed for the internal pilot study design is small and lies below the maximum excess that occurred for the fixed sample size design.     

The modified permutation entropy-based independence test of time series

Abstract

In time series, it is essential to check the independence of data by means of a proper method or an appropriate statistical test before any further analysis. Therefore, among different independence tests, a powerful and productive test has been introduced by Matilla-García and Marín via m-dimensional vectorial process, in which the value of the process at time t includes m-histories of the primary process. However, this method causes a dependency for the vectors even when the independence assumption of random variables is considered. Considering this dependency, a modified test is obtained in this article through presenting a new asymptotic distribution based on weighted chi-square random variables. Also, some other alterations to the test have been made via bootstrap method and by controlling the overlap. Compared with the primary test, it is obtained that not only the modified test is more accurate but also, it possesses higher power.     

Performance of standard imputation methods for missing quality of life data as covariate in survival analysis based on simulations from the International Breast Cancer Study Group Trials VI and VII*

Abstract

Imputation methods for missing data on a time-dependent variable within time-dependent Cox models are investigated in a simulation study. Quality of life (QoL) assessments were removed from the complete simulated datasets, which have a positive relationship between QoL and disease-free survival (DFS) and delayed chemotherapy and DFS, by missing at random and missing not at random (MNAR) mechanisms. Standard imputation methods were applied before analysis. Method performance was influenced by missing data mechanism, with one exception for simple imputation. The greatest bias occurred under MNAR and large effect sizes. It is important to carefully investigate the missing data mechanism.     

The asymptotic distribution of a pivotal quantity for a capture-recapture model

A pivotal quantity for a capture-recapture model is introduced and used to construct an asymptotic confidence region for (ε,N), where ε is the capture efficiency and N is the population size. The true confidence levels of certain regions are obtained by simulation. Certain confidence regions for (ε,N) are drawn to show the size of the regions and to show how confidence limits for N depend on ε.     

On the use of the scholz-sievers method for dlstribution-free inference about the difference in slopes of two regression lines

A simple adaptation of a distribution-free method due to Scholz (1978) and Sievers (1978) for inference in a single regression setting is proposed for inference about the difference in slopes of two regression lines. We assume that the data are obtained from a designed experiment with common regression constants. A comparison of the proposed method to its competitors-one due to Hollander and the other due to Rao and Gore-indicates superiority of the new method.     

Sensitivity analysis for two control groups

In many experiments where data have been collected at two points in time (pre-treatment and post-treatment), investigators wish to determine if there is a difference between two treatment groups. In recent years it has been proposed that an appropriate statistical analysis to determine if treatment differences exist is to use the post-treatment values as the primary comparison variables and the pre-treatment values as covariates. When there are several outcome variables, we propose new tests based on residuals as alternatives to existing methods and investigate how the powers of the new and existing tests are affected by various choices of covariates. The limiting distribution of the test statistic of the new test based on residuals is given. Monte Carlo simulations are employed in the power comparisons.