Teri Manolio: steering genomics into clinical medicine

Abstract

After almost three decades of research in genomics, Teri Manolio, Director of Genomic Medicine at the National Human Genome Research Institute (NHGRI), Bethesda, MD, USA, believes we have reached a key moment when genomics is beginning to have an impact in clinical medicine. “The area of pharmacogenomics is a good example of clinical applicability as we can help guide clinical decision making according to drug reactions that are genetically mediated”, she says. Manolio, who is a lead author of a new Lancet genomic medicine Series, sees the emerging role of genomics in clinical medicine as a natural progression in aiding clinical decision making. “As a physician with a background in epidemiology, I see genomics as providing another way of assessing risk and enabling better management of our patients, a key take-home message from the Series”, she says. Opportunities, resources, and techniques for implementing genomics in clinical careAdvances in technologies for assessing genomic variation and an increasing understanding of the effects of genomic variants on health and disease are driving the transition of genomics from the research laboratory into clinical care. Genomic medicine, or the use of an individual's genomic information as part of their clinical care, is increasingly gaining acceptance in routine practice, including in assessing disease risk in individuals and their families, diagnosing rare and undiagnosed diseases, and improving drug safety and efficacy. Full-Text PDF PharmacogenomicsGenomic medicine, which uses DNA variation to individualise and improve human health, is the subject of this Series of papers. The idea that genetic variation can be used to individualise drug therapy—the topic addressed here—is often viewed as within reach for genomic medicine. We have reviewed general mechanisms underlying variability in drug action, the role of genetic variation in mediating beneficial and adverse effects through variable drug concentrations (pharmacokinetics) and drug actions (pharmacodynamics), available data from clinical trials, and ongoing efforts to implement pharmacogenetics in clinical practice. Full-Text PDF Genomic medicine for undiagnosed diseasesOne of the primary goals of genomic medicine is to improve diagnosis through identification of genomic conditions, which could improve clinical management, prevent complications, and promote health. We explore how genomic medicine is being used to obtain molecular diagnoses for patients with previously undiagnosed diseases in prenatal, paediatric, and adult clinical settings. We focus on the role of clinical genomic sequencing (exome and genome) in aiding patients with conditions that are undiagnosed even after extensive clinical evaluation and testing. Full-Text PDF Family health history: underused for actionable risk assessmentFamily health history (FHH) is the most useful means of assessing risk for common chronic diseases. The odds ratio for risk of developing disease with a positive FHH is frequently greater than 2, and actions can be taken to mitigate risk by adhering to screening guidelines, genetic counselling, genetic risk testing, and other screening methods. Challenges to the routine acquisition of FHH include constraints on provider time to collect data and the difficulty in accessing risk calculators. Disease-specific and broader risk assessment software platforms have been developed, many with clinical decision support and informatics interoperability, but few access patient information directly. Full-Text PDF Building evidence and measuring clinical outcomes for genomic medicineHuman genomic sequencing has potential diagnostic, prognostic, and therapeutic value across a wide breadth of clinical disciplines. One barrier to widespread adoption is the paucity of evidence for improved outcomes in patients who do not already have an indication for more focused testing. In this Series paper, we review clinical outcome studies in genomic medicine and discuss the important features and key challenges to building evidence for next generation sequencing in the context of routine patient care. Full-Text PDF