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Open Access Research article

A hierarchical Bayesian network approach for linkage disequilibrium modeling and data-dimensionality reduction prior to genome-wide association studies

Raphaël Mourad1*, Christine Sinoquet2* and Philippe Leray1

Author Affiliations

1 LINA, UMR CNRS 6241, Ecole Polytechnique de l'Université de Nantes, rue Christian Pauc, BP 50609, 44306 Nantes Cedex 3, France

2 LINA, UMR CNRS 6241, Université de Nantes, 2 rue de la Houssinie're, BP 92208, 44322 Nantes Cedex, France

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BMC Bioinformatics 2011, 12:16  doi:10.1186/1471-2105-12-16

Published: 12 January 2011

Abstract

Background

Discovering the genetic basis of common genetic diseases in the human genome represents a public health issue. However, the dimensionality of the genetic data (up to 1 million genetic markers) and its complexity make the statistical analysis a challenging task.

Results

We present an accurate modeling of dependences between genetic markers, based on a forest of hierarchical latent class models which is a particular class of probabilistic graphical models. This model offers an adapted framework to deal with the fuzzy nature of linkage disequilibrium blocks. In addition, the data dimensionality can be reduced through the latent variables of the model which synthesize the information borne by genetic markers. In order to tackle the learning of both forest structure and probability distributions, a generic algorithm has been proposed. A first implementation of our algorithm has been shown to be tractable on benchmarks describing 105 variables for 2000 individuals.

Conclusions

The forest of hierarchical latent class models offers several advantages for genome-wide association studies: accurate modeling of linkage disequilibrium, flexible data dimensionality reduction and biological meaning borne by latent variables.