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Biomedical sciences publications January 1, 2009

Using Ontologies in Hierarchical Modeling of Genes and Exposure in Biologic Pathways

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Conti, D. V., Lewinger, J. P., Tyndale, R. F., Benowitz, N. L., Swan, G. E., & Thomas, P. D. (2009). Using ontologies in hierarchical modeling of genes and exposure in biological pathways. Phenotypes and Endophenotypes: Foundations for Genetic Studies of Nicotine Use and Dependence, 539-584.

Preface

Existing studies of genetic associations with nicotine dependence frequently do not reflect complex relationships between genetic, environmental, and social factors underlying tobacco use. Moreover, the scope of potential genetic variations and their impact on analysis pose a conceptual challenge to effective studies of genetic factors.

This chapter examines the potential for the use of hierarchical modeling techniques within the framework of an ontology that quantifies relationships across genotypes and phenotypes for nicotine dependence. Topics discussed include
■ An overview of the existing statistical approaches for genetic association studies
in tobacco use
■ Design and analysis considerations in the use of hierarchical modeling in
conjunction with stochastic variable selection for future genetic studies of
tobacco use
■ The use of ontologies for codifying prior knowledge to support effi cient
computational analysis of such hierarchical models
■ Results of a study of nicotine metabolism using the data from the Northern
California Twin Registry in conjunction with the Nicotine Pharmacokinetics Ontology, showing significant genetic associations with nicotine clearance levels

The results of this pilot study, and the potential of these approaches to overcome the methodological issues inherent in existing genetic studies, show promise for these approaches as an area for further study.

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