Pharmacogenetics Strategies: From Candidate Genes to Whole-Genome Association Analysis. Exploratory or Confirmatory Studies?

S.      Mas; A.      Lafuente

Abstract

In recent years the design of association studies published in pharmacogenetics journals has markedly changed and the corresponding analyses have increasingly involved a large number of SNPs, genes and patients, and a transition from the candidate gene strategy to the whole-genome association (WGA) studies. This review provides an overview of the recent advances that have led to this transition, lists the advantages and disadvantages of both strategies, candidate genes and WGA, and discusses their applicability. Another area in need of development is the standards to validate the pharmacogenetics associations observed to date. To this end, pharmacogenetics studies can also be classified as exploratory or confirmatory, independent from the design strategy used. This review discusses the importance of both types of study, exploratory and confirmatory, in ongoing efforts to replicate significant associations, and in order to provide adequate evidence for the introduction of pharmacogenetics tests in clinical practice. These different strategies or objectives (candidate genes versus WGA; exploratory versus confirmatory) are valid approaches to achieve the ultimate goal of pharmacogenetics, personalized medicine. Additionally, these nuanced differences in pharmacogenetics scientific practice must be kept in mind to ensure the appropriate evaluation of scientific merit in pharmacogenetics association studies, and their appropriate differentiation from the genetic studies concerning the disease susceptibility phenotypes.

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