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

ABSTRACT: 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 aa association study of various complication outcomes related to type 1 diabetes. This article has supplementary material online.

SUBMITTER: Xu L

PROVIDER: S-EPMC5064966 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Xu Lizhen L Craiu Radu V RV Sun Lei L Paterson Andrew D AD

Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America 20160510 2

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 e ...[more]

PMID: 27752219

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Project description:BackgroundThe ChIP-chip technology has been used in a wide range of biomedical studies, such as identification of human transcription factor binding sites, investigation of DNA methylation, and investigation of histone modifications in animals and plants. Various methods have been proposed in the literature for analyzing the ChIP-chip data, such as the sliding window methods, the hidden Markov model-based methods, and Bayesian methods. Although, due to the integrated consideration of uncertainty of the models and model parameters, Bayesian methods can potentially work better than the other two classes of methods, the existing Bayesian methods do not perform satisfactorily. They usually require multiple replicates or some extra experimental information to parametrize the model, and long CPU time due to involving of MCMC simulations.ResultsIn this paper, we propose a Bayesian latent model for the ChIP-chip data. The new model mainly differs from the existing Bayesian models, such as the joint deconvolution model, the hierarchical gamma mixture model, and the Bayesian hierarchical model, in two respects. Firstly, it works on the difference between the averaged treatment and control samples. This enables the use of a simple model for the data, which avoids the probe-specific effect and the sample (control/treatment) effect. As a consequence, this enables an efficient MCMC simulation of the posterior distribution of the model, and also makes the model more robust to the outliers. Secondly, it models the neighboring dependence of probes by introducing a latent indicator vector. A truncated Poisson prior distribution is assumed for the latent indicator variable, with the rationale being justified at length.ConclusionThe Bayesian latent method is successfully applied to real and ten simulated datasets, with comparisons with some of the existing Bayesian methods, hidden Markov model methods, and sliding window methods. The numerical results indicate that the Bayesian latent method can outperform other methods, especially when the data contain outliers.

Dataset Information

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

Publications

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

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