Author Affiliations: Dr Fontanarosa (phil.fontanarosa@jama-archives.org) is Executive Deputy Editor, Dr Pasche is Contributing Editor, and Dr DeAngelis is Editor in Chief, JAMA.
Advances in genetics and genomics are revolutionizing biomedical science and providing great promise for the future of clinical practice. The magnitude, scope, and pace of discovery in genetics and genomics research are at unprecedented levels and continue to increase exponentially. Progress in basic science resulting from the sequencing of the human genome1 and new approaches for genomics analyses have accelerated and continue to expand, resulting in new knowledge, mechanisms, and techniques for examining the genetic basis of disease. These discoveries have important implications for understanding disease processes and pathophysiology, for predicting disease susceptibility and progression, and for refining and individualizing treatments—all of which ultimately have the potential to improve health and to increase both quality of life and longevity.
Given the pace of discovery and the promise in translating these scientific discoveries to clinical application, physicians and other health care professionals must have a keen awareness about ongoing research and advances in genetics and genomics. This theme issue of JAMA is intended to provide information on genetics and genomics that is relevant and accessible for clinicians, yet also should be of interest to physician-scientists and other investigators involved in genetics and genomics research. A total of 121 manuscripts were submitted for this theme issue, resulting in far too many articles to publish in one issue. Therefore, a number of articles on genetics and genomics will be published in upcoming issues of JAMA. In addition, several members of our family of Archives Journals also are publishing theme issues on genetics and genomics, including the March and April issues of Archives of Neurology and the March issues of Archives of Dermatology, Archives of Ophthalmology, and Archives of Surgery. Additional articles on genomics and genetics are included in the March issues of Archives of GeneralPsychiatry, Archives of Internal Medicine, and Archives of Otolaryngology–Head & Neck Surgery.
In this issue of JAMA, 5 articles provide new information on genetics and genomics for common diseases and conditions, including cardiovascular disease,2 osteoporosis,3 posttraumatic stress disorder,4 venous thromboembolism,5 and cancer.6
In an elegant, comprehensive study, Bhattacharyya and colleagues2 examined the relationship among genotype, gene-related functional activity, and clinical outcomes in 1399 patients who had undergone coronary angiography. The authors found consistent associations among paraoxonase 1 (PON1) genotypes, levels of PON1 activity and systemic indices of oxidant stress, and prevalent cardiovascular disease as well as recurrent and incident cardiovascular events.
In an ambitious multicenter collaborative investigation that included individual-level data from 37Â 534 individuals from Europe and North America, van Meurs and colleagues3 studied the relationship between polymorphisms of the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) and bone mineral density and fracture risk. The authors report evidence for an association of common variants of the LRP5 gene with alterations in bone mineral density and risk of lumbar spine fractures and femoral neck fractures.
In an investigation designed to increase understanding of genetic and environmental risk factors and their potential interactions with development of posttraumatic stress disorder (PTSD) symptoms, Binder and colleagues4 examined psychological risk factors combined with single nucleotide polymorphism (SNP) genotyping in 762 primarily low-income, African American men and women. Four SNPs of the FKBP5 gene had significant interactions with severity of child abuse as a predictor of symptoms of PTSD in adults, suggesting the possibility of a gene–childhood environment interaction for adult PTSD.
In an analysis designed to examine genetic factors associated with deep vein thrombosis, Bezemer and colleagues5 analyzed 3 large case-control studies. SNPs in several genes, including CYP4V2, were associated with deep vein thrombosis and with coagulation factor XI levels, suggesting that common genetic variation is an important factor in venous thrombotic disease. As Bovill7 points out in an insightful accompanying editorial, studies such as this hold the promise that risk profiles with significant predictive value ultimately may be developed to help guide clinical practice.
In a preliminary report involving 15 asymptomatic members of families with Li-Fraumeni syndrome (which is associated with inherited predisposition to a wide array of cancers beginning early in life) and documented TP53 mutations who underwent screening with fluorodeoxyglucose–positron emission tomography/computed tomography scans, Masciari and colleagues6 identified asymptomatic cancers in 3 patients, suggesting the possibility of a cancer screening strategy for this syndrome.
Also in this issue of JAMA, 3 articles provide timely information for clinicians on current topics in genetics and genomics. Pearson and Manolio8 describe the design, interpretation, and limitations of genome-wide association studies, which should serve as a useful primer for critical assessment of reports of these investigations. Feinberg9 outlines the evolution and underpinnings of epigenetics, describing the importance of epigenetic mechanisms and approaches in developmental biology, in disease processes, and perhaps eventually, in therapy. In a systematic review of 68 studies that investigated various aspects of the delivery of genetics and genomics services, Scheuner and colleagues10 identified opportunities and challenges for clinicians, organizations, and patients that must be addressed to realize the potential benefits of genomics in clinical practice.
In addition, 4 scholarly commentaries in this issue provide insights into several current practical issues and developments in genetics and genomics. Feero and colleagues11 describe advances in genomics science and explore many of the issues surrounding translation of these advances to routine “personalized” patient care. Offit12 discusses the increasing availability of direct-to-consumer marketing of genomic and genetic testing and sounds an appropriately cautionary note about the need for standards, quality control, and appropriate regulation. Uhlmann and Guttmacher13 present a useful collection of practical Internet genetics resources for clinicians and patients, including genetics information on specific diseases; guidelines for genetic testing; and educational resources to help clinicians integrate genetics into patient care. Ginsberg and colleagues14 discuss the importance of centralized biorepositories for genetics and genomics research and emphasize the need to develop and implement standards for informed consent, informatics, and governance.
The articles in this theme issue of JAMA represent several novel findings and address several critical issues in genetics and genomics, yet illustrate only a fraction of the tremendous amount of innovative and exciting research discoveries and progress in these dynamic areas of biomedicine. We welcome other high-quality manuscripts reporting novel findings from innovative studies in genetics and genomics, with the hope of continuing to translate scientific discovery into clinical care, and with the goal of continuing to provide clinicians with important and relevant genomic information.
Financial Disclosures: None reported.
Editorials represent the opinions of the authors and JAMA and not those of the American Medical Association.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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