W. Gregory Feero

Genomic Medicine — An Updated Primer

The practice of medicine is increasingly informed by genomic discovery. This review article describes the fundamental bases of genetic and genomic discovery and launches a new series: Genomic Medicine.

The Genome Gets Personal—Almost

T’STHE“YEAROFPERFECTVISION,”2020.AMY,AGE21YEARS, visits with her physician and elects to have complete genomesequencing.Atafollow-upvisit,Amychoosesto learnofhergeneticriskfactorsforheartdisease,diabetes, breastcancer,andcoloncancer.Amy’sphysicianprovidesher with risk scores for those disorders, and with suggestions for lifestylemodifications.Specifically,Amyisalertedtoherparticularlyhighriskofdevelopingtype2diabetes,andherphy

Genomics of Cardiovascular Disease

The authors provide an overview of how genetic and genomic studies have improved our understanding of the cause of cardiovascular disease.

Genomics, Health Care, and Society

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Genomics Education for Health Care Professionals in the 21st Century

RECENT GENOMIC DISCOVERIES HAVE BROUGHT ABOUT far-reaching advances in understanding the molecular basis of human health and disease. The vision for the future of genomics research developed by the National Human Genome Research Institute suggests more discoveries are likely to occur over the next few decades. These insights have helped reveal remarkable and unexpected complexities of human biology; however, this scientific reality has slowed the immediate translation of genomic discoveries to health benefits. Nevertheless, the early implementation of genomic medicine has brought clinically important advances that rival any other period of discovery in the history of Western medicine. For example, in 1990 the genetic and molecular basis was understood for fewer than 2% of the estimated 7000 suspected mendelian conditions; in 2011, approximately 40% of mendelian conditions have a known molecular basis. This 20-fold increase in disease-gene discovery has had immediate benefits for myriad affected individuals and families who now have access to accurate diagnostic testing, and the horizon holds hope for novel treatments in many cases. Likewise, advanced genomic technologies are helping to unravel the multifaceted nature of cancer and common complex conditions, such as heart disease and diabetes. More than a thousand newly identified genetic variants have been shown to be associated with such conditions, and many of these variants point to previously unsuspected biological pathways. Although much work remains, these discoveries offer promising avenues for clinical applications informed by genomic discoveries. The appropriate use of such applications will require that clinicians be sufficiently versed in genomics to understand when it should be applied and to communicate the potential limitations and benefits to their patients. Calls for enhanced genomics education for health care professionals predate completion of the Human Genome Project. Despite this, recent evidence suggests that large segments of the physician community are not adequately trained to make appropriate use of genomic advances. This lack of training has not escaped the public’s attention: a national poll of 1000 US adults revealed that 90% lacked confidence in their clinician’s ability to understand and use genomic information. Past efforts to enhance the genomics literacy of health care professionals have often taken the form of a push of information from the genomics community to other professional groups. The underlying assumption of these efforts has been that spontaneous interest in additional genomics education would follow. The push approach has met with reasonable success in the nursing and physician assistant communities. For example, the nursing profession has internally developed genomics education competencies, which have now been broadly adopted across 50 organizations. Linking these competencies with program accreditation and individual certification has been a major driver for the incorporation of genomics into the training and continuing education of the nursing profession. However, the push approach to genomics education has not been particularly successful in physician communities. The reasons for this are complex, but can be distilled into 4 interrelated issues. First, physicians are relentlessly practical. Until recently, most genomic advances were relevant to a very small subset of clinicians; this is changing rapidly. Second, the initial fruits of genomic medicine, such as testing for hereditary cancer syndromes, arrived at a time when the health care ecosystem was under great stress. This virtually guaranteed that any new idea, unless simple and easily adopted, would face passive neglect (if not outright active resistance). Third, the clinical application of genomics does not have a tradition of adherence to the precepts of evidence-based medicine. The first forays of genomics into clinical medicine related to rare genetic diseases, for which it is often impossible to undertake large, prospective, placebocontrolled, blinded trials of diagnostics and therapeutics. Therefore, as new genomic technologies have emerged, the genomics community has often accepted them as beneficial based on little direct clinical evidence. The rapid pace of genomic discovery has compounded the problem, because clinical trials can take years to complete. Often a lack of robust evidence has impeded adoption of genomic ad-

Validation of My Family Health Portrait for six common heritable conditions.

Purpose: To assess the ability of My Family Health Portrait to accurately collect family history for six common heritable disorders.Background: Family history is useful to assess disease risk but is not widely used. We compared the pedigree from My Family Health Portrait, an online tool for collection of family history, to a pedigree supplemented by a genetics professional.Methods: One hundred fifty volunteers collected their family histories using My Family Health Portrait. A genetic counselor interviewed the volunteers to validate the entries and add diagnoses, as needed. The content and the affection assignments of the pedigrees were compared. The pedigrees were entered into Family HealthwareTM to assess risks for the diseases.Results: The sensitivity of My Family Health Portrait varied among the six diseases (67–100%) compared to the supplemented pedigree. The specificities ranged from 92 to 100%. When the pedigrees were used to generate risk scores, My Family Health Portrait yielded identical risks to the supplemented pedigree for 94–99% of the volunteers for diabetes and colon, breast, and ovarian cancer. The agreement was lower for coronary artery disease (68%) and stroke (83%).Conclusions: These data support the validity of My Family Health Portrait pedigrees for four common conditions—diabetes and colon, breast, and ovarian cancer. The tool performed less well for coronary artery disease and stroke. We recommend that the tool be improved to better capture information for these two common conditions.

Convergence of Implementation Science, Precision Medicine, and the Learning Health Care System: A New Model for Biomedical Research

This Viewpoint discusses the integration of precision medicine discoveries with the learning health care system via implementation science.

Translational research is a key to nongeneticist physicians' genomics education

described the outcomes of a workshop convened by the National Human Genome Research Institute to discuss the growing opportunities for educating nongeneticist physi-cians and other health-care providers in genomics. As a result of the workshop, an Inter-Society Coordinating Committee on Practitioner Education in Genomics was formed to facilitate interactions among professional societies intended to increase the expertise of practitioners in applying genomics in clinical care. This represents a renewed US national attempt to increase genomics competency among a key group of critical decision makers. In this commentary, we explore some of the key con-textual issues that are likely to mediate genomics educational demand and ultimately determine the success of genomics edu-cational programs for nongeneticist health professionals, espe-cially physicians.Physicians comprise a highly heterogeneous population. In the United States alone, there are 24 medical specialties recog-nized by the American Board of Medical Specialties and hun-dreds of professional societies and organizations that play a role in the educational pipeline of physicians from undergraduate education through retirement. Widespread adoption of even simple interventions with the best evidence of health bene-fits—such as ensuring that aspirin and -blockers are routinely βemployed in secondary prevention of coronary heart disease—is surprisingly difficult to attain. Genomic science and the clinical technologies that have arisen from its application are dauntingly complex, leading a former director of the National Heart Lung and Blood Institute of the National Institutes of Health to quip regarding the translation of genomic discover-ies to patient care, “If we didn’t do it with aspirin, how can we expect to do it with DNA?”

Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state‐of‐the‐science review

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first‐degree relative (FDR) increases the CRC risk 2‐fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A providers recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider‐patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high‐risk groups. Cancer 2016.

The Economics of Genomic Medicine: Insights From the IOM Roundtable on Translating Genomic-Based Research for Health

The recent exponential decline in the cost of sequencing human genomes to within an order of magnitude of