title: A hierarchical Bayesian network approach for linkage disequilibrium modeling and data-dimensionality reduction prior to genome-wide association studies.
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.
authors.affiliation: LINA, UMR CNRS 6241, Ecole Polytechnique de l'Université de Nantes, rue Christian Pauc, BP 50609, 44306 Nantes Cedex 3, France. raphael.mourad@univ-nantes.fr
authors.forename: Raphaël
authors.initials: R
authors.lastname: Mourad
authors.forename: Christine
authors.initials: C
authors.lastname: Sinoquet
authors.forename: Philippe
authors.initials: P
authors.lastname: Leray
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D005819:Genetic Markers; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers