基于全基因组的遗传性疾病和性状的关联位点分析

研究发现,通过全基因组关联分析,找出与疾病相关的位点或基因,对于人们防治遗传病,具有重要意义.首先,考虑固定效应(SNP位点)和随机效应(人群中的群体结构和亲缘关系),建立了混合线性模型,并且利用基于FDR标准的BH法对多重检验的P值进行校正,找出最有可能的致病位点.其次,利用Fisher的P值组合方法,将基因所包含的所有SNP位点组合,找出与疾病最可能相关的基因.由于遗传疾病可能与基因所包含的位点的子集关联,我们参考已有的ARTP模型,对模型进行了改进.最后,建立多表型联合模型MultiPhen找出与10个性状有关联的位点.     

A Bayesian model for repeated measures zero-inflated count data with application to outpatient psychiatric service use

In applications involving count data, it is common to encounter an excess number of zeros. In the study of outpatient service utilization, for example, the number of utilization days will take on integer values, with many subjects having no utilization (zero values). Mixed-distribution models, such as the zero-inflated Poisson (ZIP) and zero-inflated negative binomial (ZINB), are often used to fit such data. A more general class of mixture models, called hurdle models, can be used to model zero-deflation as well as zero-inflation. Several authors have proposed frequentist approaches to fitting zero-inflated models for repeated measures. We describe a practical Bayesian approach which incorporates prior information, has optimal small-sample properties, and allows for tractable inference. The approach can be easily implemented using standard Bayesian software. A study of psychiatric outpatient service use illustrates the methods.     

Parameter Expanded Algorithms for Bayesian Latent Variable Modeling of Genetic Pleiotropy Data

Motivated by genetic association studies of pleiotropy, we propose a Bayesian latent variable approach to jointly study multiple outcomes. The models studied here can incorporate both continuous and binary responses, and can account for serial and cluster correlations. We consider Bayesian estimation for the model parameters, and we develop a novel MCMC algorithm that builds upon hierarchical centering and parameter expansion techniques to efficiently sample from the posterior distribution. We evaluate the proposed method via extensive simulations and demonstrate its utility with an application to an association study of various complication outcomes related to Type 1 diabetes. This article has supplementary material online.     

Fully Bayesian Analysis of Switching Gaussian State Space Models

In the present paper we study switching state space models from a Bayesian point of view. We discuss various MCMC methods for Bayesian estimation, among them unconstrained Gibbs sampling, constrained sampling and permutation sampling. We address in detail the problem of unidentifiability, and discuss potential information available from an unidentified model. Furthermore the paper discusses issues in model selection such as selecting the number of states or testing for the presence of Markov switching heterogeneity. The model likelihoods of all possible hypotheses are estimated by using the method of bridge sampling. We conclude the paper with applications to simulated data as well as to modelling the U.S./U.K. real exchange rate.     

Conditional Logistic Regression With Longitudinal Follow-up and Individual-Level Random Coefficients: A Stable and Efficient Two-Step Estimation Method

The analysis of data generated by animal habitat selection studies, by family studies of genetic diseases, or by longitudinal follow-up of households often involves fitting a mixed conditional logistic regression model to longitudinal data composed of clusters of matched case-control strata. The estimation of model parameters by maximum likelihood is especially difficult when the number of cases per stratum is greater than one. In this case, the denominator of each cluster contribution to the conditional likelihood involves a complex integral in high dimension, which leads to convergence problems in the numerical maximization. In this article we show how these computational complexities can be bypassed using a global two-step analysis for nonlinear mixed effects models. The first step estimates the cluster-specific parameters and can be achieved with standard statistical methods and software based on maximum likelihood for independent data. The second step uses the EM-algorithm in conjunction with conditional restricted maximum likelihood to estimate the population parameters. We use simulations to demonstrate that the method works well when the analysis is based on a large number of strata per cluster, as in many ecological studies. We apply the proposed two-step approach to evaluate habitat selection by pairs of bison roaming freely in their natural environment. This article has supplementary material online.     

Objective Bayesian Model Selection in Generalized Additive Models With Penalized Splines

We propose an objective Bayesian approach to the selection of covariates and their penalized splines transformations in generalized additive models. The methodology is based on a combination of continuous mixtures of g-priors for model parameters and a multiplicity-correction prior for the models themselves. We introduce our approach in the normal model and extend it to nonnormal exponential families. A simulation study and an application with binary outcome is provided. An efficient implementation is available in the R package hypergsplines. Supplementary materials for this article are available online.     

An Empirical Comparison of Methods for Computing Bayes Factors in Generalized Linear Mixed Models

Generalized linear mixed models (GLMM) are used in situations where a number of characteristics (covariates) affect a nonnormal response variable and the responses are correlated due to the existence of clusters or groups. For example, the responses in biological applications may be correlated due to common genetic factors or environmental factors. The clustering or grouping is addressed by introducing cluster effects to the model; the associated parameters are often treated as random effects parameters. In many applications, the magnitude of the variance components corresponding to one or more of the sets of random effects parameters are of interest, especially the point null hypothesis that one or more of the variance components is zero. A Bayesian approach to test the hypothesis is to use Bayes factors comparing the models with and without the random effects in question—this work reviews a number of approaches for estimating the Bayes factor. We perform a comparative study of the different approaches to compute Bayes factors for GLMMs by applying them to two different datasets. The first example employs a probit regression model with a single variance component to data from a natural selection study on turtles. The second example uses a disease mapping model from epidemiology, a Poisson regression model with two variance components. Bridge sampling and a recent improvement known as warp bridge sampling, importance sampling, and Chib's marginal likelihood calculation are all found to be effective. The relative advantages of the different approaches are discussed.     

Bayesian comparison of models with inequality and equality constraints

A Bayesian model selection procedure for comparing models subject to inequality and/or equality constraints is proposed. An encompassing prior approach is used, and a general form of the Bayes factor of a constrained model against the encompassing model is derived. A simple estimation method is proposed which can estimate the Bayes factors for all candidate models simultaneously by using one set of samples from the encompassing model. A simulation study and a real data analysis demonstrate performance of the method.     

Bayesian adaptive Lasso

We propose the Bayesian adaptive Lasso (BaLasso) for variable selection and coefficient estimation in linear regression. The BaLasso is adaptive to the signal level by adopting different shrinkage for different coefficients. Furthermore, we provide a model selection machinery for the BaLasso by assessing the posterior conditional mode estimates, motivated by the hierarchical Bayesian interpretation of the Lasso. Our formulation also permits prediction using a model averaging strategy. We discuss other variants of this new approach and provide a unified framework for variable selection using flexible penalties. Empirical evidence of the attractiveness of the method is demonstrated via extensive simulation studies and data analysis.     

Forecasting seasonal time series data: a Bayesian model averaging approach

A flexible Bayesian periodic autoregressive model is used for the prediction of quarterly and monthly time series data. As the unknown autoregressive lag order, the occurrence of structural breaks and their respective break dates are common sources of uncertainty these are treated as random quantities within the Bayesian framework. Since no analytical expressions for the corresponding marginal posterior predictive distributions exist a Markov Chain Monte Carlo approach based on data augmentation is proposed. Its performance is demonstrated in Monte Carlo experiments. Instead of resorting to a model selection approach by choosing a particular candidate model for prediction, a forecasting approach based on Bayesian model averaging is used in order to account for model uncertainty and to improve forecasting accuracy. For model diagnosis a Bayesian sign test is introduced to compare the predictive accuracy of different forecasting models in terms of statistical significance. In an empirical application, using monthly unemployment rates of Germany, the performance of the model averaging prediction approach is compared to those of model selected Bayesian and classical (non)periodic time series models.     

Bayesian Ising Graphical Model for Variable Selection

In this article, we propose a new Bayesian variable selection (BVS) approach via the graphical model and the Ising model, which we refer to as the “Bayesian Ising graphical model” (BIGM). The BIGM is developed by showing that the BVS problem based on the linear regression model can be considered as a complete graph and described by an Ising model with random interactions. There are several advantages of our BIGM: it is easy to (i) employ the single-site updating and cluster updating algorithm, both of which are suitable for problems with small sample sizes and a larger number of variables, (ii) extend this approach to nonparametric regression models, and (iii) incorporate graphical prior information. In our BIGM, the interactions are determined by the linear model coefficients, so we systematically study the performance of different scale normal mixture priors for the model coefficients by adopting the global-local shrinkage strategy. Our results indicate that the best prior for the model coefficients in terms of variable selection should place substantial weight on small, nonzero shrinkage. The methods are illustrated with simulated and real data. Supplementary materials for this article are available online.     

Quick response policy with Bayesian information updates

In this paper we investigate the quick response (QR) policy with different Bayesian models. Under QR policy, a retailer can collect market information from the sales of a pre-seasonal product whose demand is closely related to a seasonal product’s demand. This information is then used to update the distribution for the seasonal product’s demand by a Bayesian approach. We study two information update models: one with the revision of an unknown mean, and the other with the revision of both an unknown mean and an unknown variance. The impacts of the information updates under both models are compared and discussed. We also identify the features of the pre-seasonal product which can bring more significant profit improvement. We conclude that an effective QR policy depends on a precise information update model as well as a selection of an appropriate pre-seasonal product as the observation target.     

Bayesian subset selection for threshold autoregressive moving-average models

Optimal subset selection among a general family of threshold autoregressive moving-average (TARMA) models is considered. The usual complexity of model/order selection is increased by capturing the uncertainty of unknown threshold levels and an unknown delay lag. The Monte Carlo method of Bayesian model averaging provides a possible way to overcome such model uncertainty. Incorporating with the idea of Bayesian model averaging, a modified stochastic search variable selection method is adapted to consider subset selection in TARMA models, by adding latent indicator variables for all potential model lags as part of the proposed Markov chain Monte Carlo sampling scheme. Metropolis–Hastings methods are employed to deal with the well-known difficulty of including moving-average terms in the model and a novel proposal mechanism is designed for this purpose. Bayesian comparison of two hyper-parameter settings is carried out via a simulation study. The results demonstrate that the modified method has favourable performance under reasonable sample size and appropriate settings of the necessary hyper-parameters. Finally, the application to four real datasets illustrates that the proposed method can provide promising and parsimonious models from more than 16 million possible subsets.     

Variational Approximation for Mixtures of Linear Mixed Models

Mixtures of linear mixed models (MLMMs) are useful for clustering grouped data and can be estimated by likelihood maximization through the Expectation–Maximization algorithm. A suitable number of components is then determined conventionally by comparing different mixture models using penalized log-likelihood criteria such as Bayesian information criterion. We propose fitting MLMMs with variational methods, which can perform parameter estimation and model selection simultaneously. We describe a variational approximation for MLMMs where the variational lower bound is in closed form, allowing for fast evaluation and develop a novel variational greedy algorithm for model selection and learning of the mixture components. This approach handles algorithm initialization and returns a plausible number of mixture components automatically. In cases of weak identifiability of certain model parameters, we use hierarchical centering to reparameterize the model and show empirically that there is a gain in efficiency in variational algorithms similar to that in Markov chain Monte Carlo (MCMC) algorithms. Related to this, we prove that the approximate rate of convergence of variational algorithms by Gaussian approximation is equal to that of the corresponding Gibbs sampler, which suggests that reparameterizations can lead to improved convergence in variational algorithms just as in MCMC algorithms. Supplementary materials for the article are available online.     

The determination of uncertainty levels in robust clustering of subjects with longitudinal observations using the Dirichlet process mixture

In this paper we introduce a new method to the cluster analysis of longitudinal data focusing on the determination of uncertainty levels for cluster memberships. The method uses the Dirichlet-t distribution which notably utilizes the robustness feature of the student-t distribution in the framework of a Bayesian semi-parametric approach together with robust clustering of subjects evaluates the uncertainty level of subjects memberships to their clusters. We let the number of clusters and the uncertainty levels be unknown while fitting Dirichlet process mixture models. Two simulation studies are conducted to demonstrate the proposed methodology. The method is applied to cluster a real data set taken from gene expression studies.     

Bayesian lasso binary quantile regression

In this paper, a Bayesian hierarchical model for variable selection and estimation in the context of binary quantile regression is proposed. Existing approaches to variable selection in a binary classification context are sensitive to outliers, heteroskedasticity or other anomalies of the latent response. The method proposed in this study overcomes these problems in an attractive and straightforward way. A Laplace likelihood and Laplace priors for the regression parameters are proposed and estimated with Bayesian Markov Chain Monte Carlo. The resulting model is equivalent to the frequentist lasso procedure. A conceptional result is that by doing so, the binary regression model is moved from a Gaussian to a full Laplacian framework without sacrificing much computational efficiency. In addition, an efficient Gibbs sampler to estimate the model parameters is proposed that is superior to the Metropolis algorithm that is used in previous studies on Bayesian binary quantile regression. Both the simulation studies and the real data analysis indicate that the proposed method performs well in comparison to the other methods. Moreover, as the base model is binary quantile regression, a much more detailed insight in the effects of the covariates is provided by the approach. An implementation of the lasso procedure for binary quantile regression models is available in the R-package bayesQR.     

Bayesian Sparse Group Selection

This article proposes a Bayesian approach for the sparse group selection problem in the regression model. In this problem, the variables are partitioned into different groups. It is assumed that only a small number of groups are active for explaining the response variable, and it is further assumed that within each active group only a small number of variables are active. We adopt a Bayesian hierarchical formulation, where each candidate group is associated with a binary variable indicating whether the group is active or not. Within each group, each candidate variable is also associated with a binary indicator, too. Thus, the sparse group selection problem can be solved by sampling from the posterior distribution of the two layers of indicator variables. We adopt a group-wise Gibbs sampler for posterior sampling. We demonstrate the proposed method by simulation studies as well as real examples. The simulation results show that the proposed method performs better than the sparse group Lasso in terms of selecting the active groups as well as identifying the active variables within the selected groups. Supplementary materials for this article are available online.     

Model selection of a switching mechanism for financial time series

The threshold autoregressive model with generalized autoregressive conditionally heteroskedastic (GARCH) specification is a popular nonlinear model that captures the well‐known asymmetric phenomena in financial market data. The switching mechanisms of hysteretic autoregressive GARCH models are different from threshold autoregressive model with GARCH as regime switching may be delayed when the hysteresis variable lies in a hysteresis zone. This paper conducts a Bayesian model comparison among competing models by designing an adaptive Markov chain Monte Carlo sampling scheme. We illustrate the performance of three kinds of criteria by comparing models with fat‐tailed and/or skewed errors: deviance information criteria, Bayesian predictive information, and an asymptotic version of Bayesian predictive information. A simulation study highlights the properties of the three Bayesian criteria and the accuracy as well as their favorable performance as model selection tools. We demonstrate the proposed method in an empirical study of 12 international stock markets, providing evidence to strongly support for both models with skew fat‐tailed innovations. Copyright © 2016 John Wiley & Sons, Ltd.     

Annealed Importance Sampling Reversible Jump MCMC Algorithms

We develop a methodology to efficiently implement the reversible jump Markov chain Monte Carlo (RJ-MCMC) algorithms of Green, applicable for example to model selection inference in a Bayesian framework, which builds on the “dragging fast variables” ideas of Neal. We call such algorithms annealed importance sampling reversible jump (aisRJ). The proposed procedures can be thought of as being exact approximations of idealized RJ algorithms which in a model selection problem would sample the model labels only, but cannot be implemented. Central to the methodology is the idea of bridging different models with fictitious intermediate models, whose role is to introduce smooth intermodel transitions and, as we shall see, improve performance. Efficiency of the resulting algorithms is demonstrated on two standard model selection problems and we show that despite the additional computational effort incurred, the approach can be highly competitive computationally. Supplementary materials for the article are available online.