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The emergence of a new paradigm of pharmacogenomics.

A series of qualitatively new properties of the complex polygenic systems are transforming the dominant, genome-centric approach of pharmacogenomics towards a more integrative, holistic paradigm. The recent concepts of interposition of regulatory networks between genotype and phenotype, and the emergence of epigenotype as the locus of integration of genetic background with nutritional and lifestyle influences, render problematic any prediction of the consequences of individual gene alterations. In addition, the redefinition of the traditional boundaries of clinical phenotypes, with the promotion of the endophenotypes as methodological strategy, and the initiative of the phenome elucidation, reshape both the research, as well as the application, of pharmacogenomics. These concepts and developments can explain some of the complexity, and the multifactorial nature, of most drug responses and imply another understanding of education in the field, which aims at stimulating a critical reflection on these major shifts prior to a practical training on the immediate application of pharmacogenomics.