GENOMIC BASIS OF PHARMACOGENETICS Phenotype

Pharmacogenetics is the study of the genetic basis for variation in drug response. In this broadest sense, pharmacogenetics encompasses pharmacogenomics, which employs tools for surveying the entire genome to assess multigenic determinants of drug response. Until the technical advances in genomics of the last few years, pharmacogenetics proceeded using a forward genetic, phenotype-to-genotype approach. Drug response outliers were compared to individuals with “normal” drug response to identify the pharmacologic basis of altered response. An inherited component to response was demonstrated using family studies or imputed through intravs. intersubject reproducibility studies. With the explosion of technology in genomics, a reverse genetic, genotype-to-phenotype approach is feasible whereby genomic polymorphisms can serve as the starting point to assess whether genomic variability translates into phenotypic variability.