Relating human genetic variation to variation in drug responses

Abstract

Although sequencing a single human genome was a monumental effort a decade ago, more than 1000 genomes have now been sequenced. The task ahead lies in transforming this information into personalized treatment strategies that are tailored to the unique genetics of each individual. One important aspect of personalized medicine is patient-to-patient variation in drug response. Pharmacogenomics addresses this issue by seeking to identify genetic contributors to human variation in drug efficacy and toxicity. Here, we present a summary of the current status of this field, which has evolved from studies of single candidate genes to comprehensive genome-wide analyses. Additionally, we discuss the major challenges in translating this knowledge into a systems-level understanding of drug physiology, with the ultimate goal of developing more effective personalized clinical treatment strategies.

Figure 1. The evolution of pharmacogenomics

The diagram depicts the different advantages and disadavantages for candidate gene approaches, candidate pathway genes approaches, genome-wide association studies (GWAS), and next-generation sequencing. New techniques (e.g., GWAS) do not necessarily replace old strategies (e.g., candidate gene approach). Examples of the candidate gene approach include the gene/drug pairs (UGT1A1/Irinotecan). Examples of GWAS include the gene/drug pairs (/IL28B/Peginterferon alfa-2b).