The science of medicine and the practice of medicine (that is, the provision of healthcare) are distinct domains. Our burgeoning knowledge of the human genome is beginning to transform the former, and there are already examples where genomic information is now part of the standard of care62,63,64. Genomic discoveries will increasingly advance the science of medicine in the coming decades (Fig. 2), as important advances are made in developing improved diagnostics, more effective therapeutic strategies, an evidence-based approach for demonstrating clinical efficacy, and better decision-making tools for patients and providers. Realistically, however, a substantial amount of research is usually needed to bring a genomic discovery to the bedside, as initial findings indicating potential benefits must be followed by clinical studies to demonstrate efficacy and effectiveness65.

Diagnostics

Over the next decade, the variant genes responsible for most Mendelian disorders will be identified and, for some number, such knowledge will lead to the development of practical treatments. A more immediate benefit will be an accurate diagnosis that, even in the absence of a treatment, can be clinically valuable. A rapid, accurate diagnosis cuts short the ‘diagnostic odyssey’ that often involves many false leads and ineffective treatments, can reduce healthcare costs, and provide psychological benefit to patients and families.

Beyond Mendelian disorders, a major benefit of genomic (and other ‘-omic’) information will come from accurate subclassification of diseases. As shown for breast cancer19, understanding the ‘molecular taxonomy’ of a disease can help distinguish different conditions that have common pathophysiological or morphological features, yet respond to different treatments.

Therapeutics

Genomic information can be used in many ways for developing improved therapeutics. The following discussion focuses on pharmaceuticals, where genomic information can inform target identification, rational drug design, genomics-based stratification in clinical trials, higher efficacy and fewer adverse events from genotype-guided drug prescription (pharmacogenomics), as well as guide the development of gene therapy strategies. Genomic information will also inform therapeutic approaches based on dietary, behavioural and lifestyle interventions, modification of environmental exposures, and other population-based or societal interventions that have genotype-specific effects66,67,68.

The systematic development of a pharmaceutical requires the discovery and validation of a disease-relevant target in the relevant cells. Traditionally, targets have been identified biochemically, one at a time. The more thorough understanding of disease potentiated by genomics will bring extraordinary opportunities for identifying new targets for drug development69. Using detailed information about a disease, candidate therapeutic agents (for example, small molecules, antibodies and other proteins, and small interfering RNAs) can be identified by high-throughput screening methodologies or developed by molecular design technologies. It must be noted, however, that many of the subsequent steps in drug development (for example, medicinal chemistry, pharmacokinetics and formulation) do not involve genomics, and cannot be expected to be improved by it. The development of new pharmaceuticals based on genomic knowledge of specific targets and their role in disease has already been markedly successful70,71,72,73, and is becoming increasingly commonplace, particularly for cancer drug development74,75.

At the same time, understanding the underlying disease biology based on genomic information does not guarantee new therapeutics. For example, although some human disease genes (such as those for sickle cell anaemia, Huntington’s disease, and cystic fibrosis) were identified more than two decades ago, the development of suitable therapies for these disorders has been much slower than anticipated. Although there have been recent promising developments13,76, success is by no means certain in all cases.

Another significant opportunity offered by genomics is improved design of clinical trials77. Currently, many clinical trials treat the tested population as genetically homogeneous. But stratification of trial participants using genomic information can allow the use of smaller numbers of participants and increase statistical power for establishing effectiveness and reducing morbidity. An example is gefitinib, for which survival benefit was only documented by analysis in a genomically selected population78. Genomics should also allow the identification of individuals genetically susceptible to adverse reactions79. Correlation of genomic signatures with therapeutic response will enable the targeting of appropriate patients at appropriate stages of their illness in clinical trials, resulting in more effective drugs as well as better dosing and monitoring. It will also significantly affect the information provided to prospective research participants regarding the potential for medical benefit directly related to trial participation, a topic of intense controversy for early-phase clinical trials80.

Pharmacogenomics is another direct clinical application of genomic medicine. Genetically guided prescription of the antiretroviral drug abacavir is now the standard of care for HIV-infected patients81, and it is likely that the use of tamoxifen82, clopidogrel83 and possibly warfarin84 will soon benefit from genetic considerations. Realistically, however, pharmacogenomics will not be useful for all drugs, such as those for which metabolism is not affected by genetic variation or for which there are redundant metabolic pathways. As in any other area of medicine, actual patient benefit must be demonstrated before routine clinical use of a pharmacogenomic test65.

An evidence base for genomic medicine

The effectiveness of genomic information in tailoring interventions and, ultimately, improving health outcomes must be demonstrated. Genomically informed interventions (for example, pharmacogenomic tests or the use of genomics-based information to change risk behaviour) must be evaluated with a portfolio of research approaches, including retrospective analyses, prospective studies, clinical trials and comparative effectiveness studies, to evaluate their impact on decision making, health outcomes and cost. This will also help to avoid harm to patients or the wasting of time and resources68. However, although a substantial evidence base before clinical introduction is ideal, there can be costs in delaying the implementation of useful genomics-based strategies. In some situations, genomic information may provide opportunities to develop and use innovative clinical trial designs that lead to provisional approval with continued study. Informed and nuanced policies for healthcare payer coverage could also facilitate provisional implementation while definitive data are accrued.

Genomic information and the reduction of health disparities

Most documented causes of health disparities are not genetic, but are due to poor living conditions and limited access to healthcare. The field of genomics has been appropriately cautioned not to overemphasize genetics as a major explanatory factor in health disparities85. However, genomics research may still have a role in informing the understanding of population differences in disease distribution, treatment response and the influence of gene–environment interaction and epigenomics on disease and health86,87. For example, a few genetic variants can be correlated with population differences associated with an increased risk for several diseases with documented prevalence disparities, such as prostate cancer88 and kidney disease89. Although the results of most genomic studies will apply broadly, it is important to identify any specific genetic factors that may be associated with disparate disease risk, incidence, or severity among population groups.

Barriers to obtaining the benefits of genomics need to be identified and addressed. It will be important to recognize and understand how genomics researchers and research participants conceptualize and characterize human groups and whether or how such categorizations shape research outcomes. Many group-based social identities, most notably those reflecting race, ethnicity and nationality, include ancestry and morphology as bases of categorization90. When analysing phenotypic data, innovative approaches will be needed to tease apart the many confounders that co-vary with social identity. Progress in parsing the interactions among multiple genetic, environmental and social factors promises to provide more accurate predictions of disease risk and treatment response. Most importantly, as genomics continues to be applied in global healthcare settings, it must not be mistakenly used to divert attention and resources from the many non-genetic factors that contribute to health disparities, which would paradoxically exacerbate the problem.

Delivering genomic information to patients

The routine use of genomics for disease prevention, diagnosis and treatment will require a better understanding of how individuals and their healthcare providers assimilate and use such information. The amount and heterogeneous nature of the data, which will include both expected and unexpected results, will antiquate current mechanisms for delivering medical information to patients.

Healthcare professionals will need to be able to interpret genomic data, including those from direct-to-consumer services, that are relevant to their scope of practice and to convey genetic risk to their patients. Patients will need to be able to understand the information being provided to them and to use that information to make decisions. Implementation research will help define the best ways to convey the uncertainties and complexities of genomics-based risk information to individuals and their families, how such information is understood, and how it influences health-related behaviour. Principles should be developed for guiding decisions about acquiring genomic information. These principles will have to balance the potential benefits of new preventive measures and therapeutics with economic impact and the potential for harm.

Achieving effective information flow will require an understanding of the issues related to achieving genomic medicine literacy by healthcare providers and consumers (Box 4) and the influence of genomic information on an array of health behaviours68. Additional research should investigate the impact of various factors (for example, family history and underlying motivations) on patients’ ability to reduce their risk. Here too, evidence-based best practices are needed to ensure that patients have adequate information, access to appropriate healthcare services, and suitable follow-up to help them use their genomic information. These best practices should also inform the development and implementation of evidence-driven regulatory policies that enhance the public benefit of genomics, but at the same time protect the public from inaccurate claims and the dissemination of unreliable information.

Additional challenges will arise as genomics becomes part of global medicine. Strategies that take into account differences in healthcare practices and systems will be required to realize the potential of genomics to prevent and treat disease around the world.