Whole-Genome Sequencing Informs Treatment: Personalized Medicine Takes Another Step Forward

Personalized medicine has long been a key therapeutic goal, harnessing the best treatments for an individual to maximize benefit while minimizing risk. Approaches to achieving such personalized therapy have included analyses of specific genes with therapeutic implications in specific disorders, such as the analysis of genetic testing of polymorphisms in CYP2C19 3 (cytochrome P450, family 2, subfamily C, polypeptide 19) in individuals being prescribed clopidogrel, as discussed in a recent Perspective article in this journal (1). In my own clinical area of neurology, a recent report stated that the effect of the drug entacapone, which inhibits catechol- O -methyltransferase, in prolonging the effectiveness of l-dopa in Parkinson disease is enhanced in patients with specific polymorphisms in this enzyme (2). The time when we routinely screen for certain genetic variants in specific genes before starting therapies will surely not be far off. In the next phase, with DNA-sequencing costs decreasing further and advances in computing methods for sequence analysis pushing ahead, whole-genome sequencing (WGS)4 is poised to take personalized medicine a stage further. Within a year or two, physicians may be presented with patients armed with their full genetic profiles, seeking advice about the best treatments for their specific circumstances.In the last few months, 2 specific reports have caught my eye, both of which illustrate how the use of WGS has already directly produced beneficial change in patients' clinical management. The first report is from a study by Bainbridge et al. published in Science Translational Medicine (3), in which WGS was used to first identify the genetic basis for a disorder in a family, in this case l-dopa–responsive dystonia (DRD), and then to provide a rationale for a specific treatment intervention. Dystonia is the term used to describe a clinical disorder of sustained muscle contractions with repetitive …