Genomic medicine is an approach to medical diagnosis, treatment, and risk assessment based on an individual’s genome (genetic make-up) and gene expression patterns. The past decade has been a time of research and discovery for genomic medicine (a.k.a. personalized medicine, individualized medicine, precision medicine, molecular medicine). Scientists involved in translational research are using collaborative methods in an effort to accelerate the development of useful clinical tools.
As the science is propelled forward by rapid advances in technology, genomic procedures affecting every medical specialty will become an important part of medical practice. An area that spans all specialties is pharmacogenomics, which includes tests able to detect genetic variations that are associated with high risk of abnormal response to certain drugs (from nonresponse to toxic response). Pharmacogenomic knowledge gaps and educational resource needs have been identified among physicians which threaten to delay the implementation of these potentially useful tests. Click here to read a 2014 article available from PubMed Central that reviews this issue.
This web portal is designed to give physicians and other healthcare professionals easy access to relevant genomic medicine information and resources. We hope that the portal will be a useful tool to physicians, nurses, pharmacists, and other clinical healthcare providers as they begin to apply evidence-based genomic approaches to improve patient outcomes.
For help in figuring out a plan to learn more about genomic medicine, see our list of 11 How-to-Get-Started Tips
For an overview of advances in 2015, read From Genomic Medicine to Precision Medicine: Highlights of 2015, published in Genome Medicine on 1/29/2016
For perspective on why you should be interested in advances in genomic medicine, click on your specialty . . .
Orthopedics & Rheumatology
Anesthesiologists are beginning to turn to genomic medicine to reduce the risk of perioperative organ injury. Topics of interest include identifying key genetic variants associated with adverse events following major surgery, understanding their mechanism of action, using this information to identify individuals at risk for specific postoperative cardiac events, and designing personalized cardioprotective interventions. Duke University School of Medicine’s Anesthesiology Department is studying Systems Modeling of Perioperative Cardiovascular Injury & Adaption “with the ultimate goal of designing and testing prospective, preventive and personalized cardioprotective interventions through the application of genomic technologies.”
Many recent studies point to specific DNA variants and genes such as LPA, CXADR, and APOE as key genetic markers for susceptibility to coronary artery disease and sudden cardiac death. A number of variants are associated with a 2-fold increase in risk for coronary artery disease, myocardial infarction, and ventricular fibrillation. Genetic variants in mediators of the clopidogrel antiplatelet response are associated with a greater than 3-fold increase in risk for stent thrombosis. As more genetic associations with disease pathogenesis and drug response are identified and translated into clinical utility, we are likely to see radical changes in the practice of cardiovascular medicine. See: Damani SB & Topol EJ. Emerging genomic applications in coronary artery disease. JACC Cardiovasc Interv, 2011 May;4(5):473-82. PMID 21596318
Increased understanding of how genes and chromosomes change during the aging process will enable dermatologists to better advise their patients on optimal skin care. These genetic insights will spur the development of methods to delay or reverse aging processes, leading to improved skin care treatments. See: http://www.aad.org/stories-and-news/news-releases/understanding-the-science-of-good-genes-could-lead-to-better-skin-care-products-recommendations
The most common mutation found in melanoma occurs in the RAS pathway gene BRAF. Recently, the SETDB1 gene was found to encode an enzyme that interacts with BRAF to markedly accelerate melanoma onset. SETDB1 is potentially both a prognostic marker and a therapeutic target. See: http://www.aad.org/dermatology-world/monthly-archives/2011/june/finding-in-fish-offers-potential-explanation-for-melanoma-formation
In 2009, the NIH Medical-Surgical Emergency Research Roundtable was convened to discuss research priorities and challenges for emergency care. Rapidly identifying the phenotype and genotype of patients manifesting a specific disease process and determining the mechanistic reasons for heterogeneity in outcome were identified as important challenges for emergency care research. See: PMID 21036293
Asthma is a good example of how genomic information may become part of clinical practice in emergency settings. An ER physician who is presented with a child undergoing an asthma attack may be informed by a parent that the child has the “steroid gene.” The physician will know to look for previous genomic test results indicating reduced sensitivity to glucocorticoid treatment, and prescribe higher doses and longer treatment. See: Freishtat RJ & Teach SJ. Understanding genomics: Implications for the emergency medicine physician and the treatment of asthma. Pediatr Emerg Care. 2006 January;22(1):71-78. PMID 16418618
Genomic research has led to a better understanding of the molecular mechanisms of endocrine disorders. Recent discoveries include genes that encode for new hormones (e.g., leptin), genes that play critical roles in development (e.g., sexual differentiation, development of the pituitary gland), and tumor suppressor gene mutations that may promote development of multiple endocrine neoplasia type 1. One outcome is the identification of novel targets for creating new therapeutic agents (e.g., synthesis of kinase inhibitors to potentially treat thyroid tumors). See: Tenore A & Driul D, Genomics in Pediatric Endocrinology – Genetic Disorders and New Techniques. Pediatr Clin N Am. 2011; 58(5):1061-81. PMID 21981949
The goal of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) is to promote fundamental understanding of disease mechanisms, including the roles of genetic variation and regulation, as a platform to advance treatments in the clinic. One example is the use of molecular endocrinology tools to show that dysregulation of hormone and cytokine release from adipose tissue contributes to the development and progression of obesity, diabetes, and other metabolic diseases. See: Margolis R & Smith P, Commentary: Parallel Evolution of Molecular Endocrinology as a Journal and a Discipline. Mol Endocrinol. 2010 Sept; 24(9):1697-702. PMID 20660301
The American Academy of Family Physicians (AAFP) has a topics page devoted to Genetics Resources. It has links to articles on counseling, testing, and risk assessment.
Models for integrating genetic services into the health care system are discussed in a 2012 review in Public Health Genomics, “Genetics in health care: an overview of current and emerging models.” One model is to refer rare disorders (such as cystic fibrosis) to dedicated multidisciplinary clinics, which would offer coordination and information-sharing with primary care physicians and partnerships with families and support groups. Common diseases (such as cancer genetics) would be handled in a collaborative model (multiple specialists, allied health professionals, and community members) that uses multi-step procedures for risk assessment, testing, counseling, and care.
The 4 highest priorities identified by the Future Trends Commmittee of the American Gastroenterological Association (AGA) in 2004 were: (1) new colorectal cancer screening and diagnostic technologies, (2) obesity-related disease, (3) aging of the population, and (4) genomic and proteomic technologies. Significant progress has been made in understanding the genetic causes of simple Mendelian diseases such as familial adenomatous polyposis (FAP), hereditary hemochromatosis, and hereditary pancreatitis. With the genomic tools now available, researchers are beginning to dissect causes of common complex diseases such as irritable bowel syndrome (IBS), nonalcoholic fatty liver disease, and inflammatory bowel disease (IBD). A wide range of potential applications are anticipated in the future, such as using genetic variants to identify disease sucsceptibility or predict individual responses to specific treatment regimes. See: PMID 16285969
Medical geneticists will undoubtedly play a major role in the future of genomic medicine. Traditionally, geneticists have provided comprehensive diagnostic, management, and counseling services for patients with rare genetic disorders. Large-scale genomic technologies are anticipated to extend the work of geneticists to virtually every aspect of medicine. Medical geneticists will need to embrace an expanded role to survive in a big-data, genome-centric future. Front-line medical providers, including primary care physicians and all medical specialties, will need to improve their genetic/genomic literacy. Yet few will have the time or ability to handle the complexities of comprehensive genetic testing and risk assessment. The expertise and assistance of knowledgeable geneticists will therefore be critical to the successful implementation of genomic medicine. See: “Medical Genetics in the Genomic Medicine of the 21st Century” by Epstein CJ, Am J Hum Genet. 2006 Sep;79(3):434-8. PMID 16909381 ~ Free full text article
In the study of trauma biology and sepsis, the field of functional genomics and its genome-wide expression analysis tools have enabled the development of molecular signatures for inflamed tissues and specific cell populations. These are being used to classify the progress of disease and survival in response to traumatic and burn injury, sepsis and visceral ischemia, and reperfusion injury. Patterns of gene expression in response to varying microbial pathogens are also being characterized. Functional genomics is beginning to reveal the underlying complexity of the biological response to a variety of inflammatory diseases. See: PMID 16237642
Systematic molecular biology studies using genomics information and technologies have helped to elucidate mechanisms of virulence and pathogenicity. Genomics-based medical genetic studies have been used to better understand pathogen susceptibility. This progress may lead to the development of effective and safe vaccines in the future. See: PMID 18767959
The epidemiology, pathogenesis, and/or therapeutics of virtually every infectious disease are almost certainly influenced by human genomics, an influence that is exemplified by HIV-1. See: PMID 17492588 ~ Free full text article
Enormous progress is being made by using advanced molecular genetic tools to analyze the genetic architecture of common diseases, including diabetes, osteoporosis, and cardiovascular disorders. Although new disease pathways are being discovered, they have not yet reached the point of practical applications. On the other hand, pharmacogenomics has entered day-to-day clinical practice. Specific genetic markers help physicians to determine optimal dosing and/or predict toxicity for a variety of drugs, including warfarin, abacavir, 6-mercaptopurine, irinotecan, carbamazepine, and tricyclic antidepressants. See: PMID 18947300
Researchers at Brigham and Women’s Hospital are collaborating with their colleagues at Boston Children’s Hospital in a randomized controlled trial to start collecting blood samples from newborn infants in order to sequence their entire genome. The BabySeq project began in May 2015 and the estimated completion date of this 3-year project is August 2018. See: The BabySeq Project | G2P . . . and Genomic Sequencing for Childhood Risk and Newborn Illness | Clinical Trials
Combining samples from a national neonatal screening program with the information from a national health registry provides unique opportunities for detection of protein changes in newborns’ blood that could predict eventual disease development. A nested case-control cohort in Denmark was analyzed using a proteomics approach as a new way of identifying biomarkers to improve prediction of type 1 diabetes risk in newborns. See: PMID 20878220
Since its inception, newborn screening (NBS) has saved thousands of children from the effects of devastating genetic diseases. Next-generation sequencing technology will enable the detection of a larger number of deleterious genetic variants, thereby expanding the number of pediatric disorders evaluated without substantially increasing the costs of NBS. However, ethical and practical concerns require ongoing discussion among screening program managers, genome scientists, primary care physicians, and parents in order to assess where and how these technologies should be used. See: PMID 22298675
The multi-center Family Investigation of Nephropathy of Diabetes (FIND) Consortium aims to identify genes for diabetic nephropathy (DN) and its associated quantitative traits (urine albumin:creatinine ratio, etc.). DN contributes to approximately 50% of incident cases of end-stage renal disease. Studies using genomewide linkage scans support the view that genetic factors contribute to DN and albuminuria. See: PMID 21454968
With continued technological advances and development of new analytic methods, additional genetic variants and mechanisms will be identified and help to clarify the pathogenesis of DN. These advances will lead to early detection and development of novel therapeutic strategies to decrease the incidence of disease. See: PMID 22573336
Neurological diseases comprise a vast range of diseases that vary in severity, age of onset, clinical presentation, genetic influence, and therapeutic response. Many have a specific genetic basis. The substantial number and variety of neurological conditions for which genomic variation plays a role in the susceptibility, course, and/or treatability of disease makes this an exciting class of disorders to consider in the context of genomic medicine. There have been recent achivements in genomic medicine in many neurological conditions, including nervous system cancer and tumor syndromes, stroke, deafness, dementia, Parkinson disease, autism, intellectual disability, pain, epilepsy, multiple sclerosis, Charcot-Marie-Tooth disease, spinal muscular atrophy, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis. See: PMID 21594611 ~ Free full text article/good review
A host of system-wide “omics” approaches – genomics, transcriptomics, proteomics, and metabolomics – are currently revolutionizing how we think about, diagnose, and treat disease and injury. Clinical neuroproteomics is a subfield of proteomics that seeks to develop a better understanding of human central and peripheral nervous system disease and injury, and to discover neurological protein biomarkers of pathology. Few biomarkers have been approved yet by the Food and Drug Administration for routine use. Translation of this basic research into effective clinical applications is a major goal. See: PMID 21866062
A core component of nursing education is to provide an understanding of the complex pathophysiology of human disease. Scientists, pharmacists, physicians, and nurses involved in the translational medicine continuum (developing laboratory-based discoveries into useful patient applications) continue to apply the science that evolved from the Human Genome Project to uncover risk factors, develop biomarkers, and tailor medication dosage to improve patient care. A 2011 article in Annual Review of Nursing Research, Molecular genomic research designs explains the rationale for taking various approaches to genomic research (candidate gene association, genome-wide association, candidate gene expression, global gene expression, epigenetic/epigenomic).
Specialty nursing areas are also encouraging nurses to develop an understanding of how genomic medicine impacts their patients. The 2013 Oncology Nursing Society Position statement, Oncology Nursing: The application of cancer genetics and genomics throughout the oncology care continuum is a good example of this trend, driven by specialty nursing organizations.
Calprotectin (S100A8/A9) is a calcium- and zinc-binding protein found mainly in neutrophils and to a lesser extent in monocytes and macrophages. It has multiple properties (antimicrobial etc.), and participates in many physiological and pathological conditions relevant to obstetrics and gynecology, including: breast, ovarian, endometrial, and cervical cancers; cervical and vaginal physiology, menstrual cycle, pregnancy, and labor; and intra-amniotic inflammation, preeclampsia, HELLP syndrome, and Rh- incompatibility. Elucidating the roles and regulation of calprotectin through the use of molecular and genomics tools will allow physicians to better understand, diagnose and treat many of these conditions. See: PMID 20378239
Molecular data indicate that the novel protein urocortin could play a significant role in human reproduction (steroidogenesis in the ovary, maintenance of placental function, and labor). Further investigation is necessary to clarify the physiological pathways in which urocortin participates. See: PMID 18777033
Chromosomal microarrays may be a useful adjunct to conventional karyotyping when evaluating genomic imbalances in women with premature ovarian failure. See: PMID 21256485 ~ free full text article
In “The Challenge and Promise of the Genomic Era” (presidential address, 2011 annual meeting of the American Society of Clinical Oncology), Dr. George Sledge stated that several thousands of cancers covering 20 major tumor types were being sequenced at that time. Large-scale tumor sequencing programs will rapidly change our understanding of cancer biology, identify new targets in previously hard-to-treat diseases, and explain the causes of drug resistance. By the end of this decade, we may see the beginning of population-based deep sequencing of patients’ tumor genomes. Data from host and tumor genomics studies will lead to an individualized understanding of risk and benefit. One of the challenges will be to change the current clinical trial mechanism from an emphasis on single agent trials into a pathway that can handle multiple biomarker-driven studies. Dr. Sledge called this “genomic chaos” and described our regulatory apparatus as “ill suited to the emerging biologic reality.” See: PMID 22162574
Molecular medicine has a tremendous potential to be applied to the diagnosis and treatment of ophthalmic disorders (Ocular Genomics Institute website, Massachusetts Eye and Ear Infirmary & Harvard Medical School). Clinical trials have demonstrated the successful use of ocular gene therapy to treat the RPE65 form of Leber congenital amaurosis (LCA). Progress has been made in identifying the genetic basis of retinal degeneration and other ophthalmic disorders. Glaucoma is the leading cause of irreversible blindness worldwise, with primary open angle glaucoma (POAG) being the most common subtype. Recent studies show that POAG patients carrying identified glaucoma risk alleles tend to be diagnosed with the disease several years earlier than patients without these alleles. Further longitudinal studies will investigate whether TMCO1 genotyping can predict severity or progression of glaucoma. See: PMID 22714896
Advances in the identification of risk factors for oral cancer and a molecular picture of its pathoprogression suggest that this disease may be preventable to a certain extent. With the development of cutting-edge molecular genetic tools, these advances have prepared a pathway for easier diagnosis, better prognostication, and efficient therapeutic management. See: PMID 22654364 ~ free full text article
About 90% of individuals with oral cancer are diagnosed with oral squamous cell carcinomas (OSCC) arising from the mucosal lining, with about 50% dying from that disease. It has been fairly well established that these cancers arise as a consequence of the accumulation of genetic alterations in proto-oncogenes and tumor supressor genes, a process referred to as multistep carcinogenesis. Recent technologic developments have enabled simultaneous screening of copy number imbalances in multiple genomic regions. The identification of novel therapeutic targets and the key molecular determinants of tumor biology will lead to improved understanding and treatment of these devastating tumors. See: PMID 21334929
Genome-wide association studies (GWAS) have been successful in identifying new osteoarthritis (OA) genes. A more powerful genetic analysis will be reached in future studies that combine increasing sample size and refinement of the OA-phenotypes. As next-generation sequencing (NGS) matures, the ability to fully sequence genomes at the basepair level will take genomic science to the next level. A better understanding of DNA sequence variation will be obtained with NGS. When this is combined with dynamic data obtained through new approaches in epigenomics and transcriptomics, the result will be new insights into the relationship between genotype and OA-phenotypes of this complex condition, opening up new avenues for targeted therapy. See: PMID 22917744
Advances in genomic science have made their effects felt in numerous areas of ENT, including hearing loss, sinusitis, and fine needle aspiration (FNA). A genetic approach to hearing loss requires the traditional otologic, audiologic, family history and physical examination to be combined with ancillary and molecular genetic testing, access to electronic databases, and collaboration with genetics professionals. See: PMID 22115680
Diseases within the sinuses affect approximately 16% of the population. In recent years, chronic sinusitis (CS) has become identified as a spectrum of disorders, often with overlapping features. Further work is needed to identify diagnostic biomarkers for each subgroup that can be used in the clinical setting. See: PMID 21704364
In laryngology, the combination of FNA with genomics technologies provides the means of obtaining clinically useful information about benign and malignant disease from only a small number of cells. See: PMID 16806815
Palliative medicine is an area in which comprehensive knowledge of individual genome status could be of extreme clinical interest, as it could be incorporated into practical guidance of clinical interventions. For instance, genetic heterogeneity in inflammation-related genes influence pain perception and the degree of analgesia obtained with different methodologies in cancer patients. Interpersonal variation in opioid response is large, and genetic determinants of opioid sensitivity have been extensively identified. As well, much of the individual variability in response to morphine is determined by genetic variation. Genetic variation in transport proteins impacts the absorption, distribution, and elimination of drugs. By having a better understanding of an individual’s genetic background and connecting it with phenotypical observations in patients undergoing palliative care, caregivers should be able to move to preventive interventions (early anti-inflammatory drug administration, hormonal therapy, exercise for patients at high risk for loss of lean body mass, regular screening for patients at higher risk for delirium, and early opioid rotation for patients likely to develop rapid tolerance). See: PMID 21075271
Representatives from major national pathology organizations held a stakeholder summit at the Banbury Conference Center, Cold Spring Harbor Laboratory, New York in October 2010. Their agenda concerned genome-era pathology, precision diagnostics, preemptive care, and the future role of pathologists in the rapidly developing field of personalized medicine. Three fundamental themes emerged from the discussions, including (1) the “opportunity for pathologists to be curators of genomic information during the course of each person’s lifetime, providing up-to-date interpretations of genomic information in the context of intercurrent health events and needs,” (2) the need to “establish pathology’s primary place in genome-era medicine” and “acquire and demonstrate expertise in this rapidly evolving era of personalized and patient-centered health care,” and (3) the necessity to “demonstrate that the involvement of pathologists in the provision of medical care informed by genomic information improves patient health outcomes and is a more cost-effective way of providing personalized health care than current practices that depend on testing for individual molecular deviations.” See: Report of the Proceedings, AJCP, 2011 and Lecture Materials from Training Pathology Residents in Genomics
Advances in statistical models, technology, and software have transformed the field of genomics. Developing in parallel are a range of new approaches in the areas of epigenomics, proteomics, transcriptomics, and replication profiling, all of which offer unprecedented insight into how the genome functions and is regulated. It will be a complex but necessary task to integrate these areas in order to fully understand the biology of complex disease. An increasing number of rare syndromes are being resolved, and clinical tests are available to diagnose idiopathic forms of intellectual disability, neuropsychiatric subtypes, and congenital malformations. As the genome era emerges from its infancy, the relationship between genotype and phenotype will become delineated, with a deeper understanding of pediatric development and diseases. This will open up new avenues for targeted therapies for patients with variations that are most likely to be responsive based on functional pathways impacted by genetic variations. See: PMID 22566424
The area of pharmacogenomics is one of the fastest developing areas of genomic medicine. Biomarkers that identify risk factors to medication tolerance and adverse reactions need to be understood by pharmacists who work as a team with prescribing physicians. A 2013 article in Clinical Pharmacology & Therapeutics, Educational challenges in implementing genomic medicine highlights the importance of educating the pharmacy workforce in order to prevent errors of omission and commission as genotyping reveals risk factors related to medication-specific biomarkers.
From 1993 to 2004, only 8% of central nervous system drug candidates that reached the stage of initial human testing eventually achieved regulatory approval, primarily due to an inability to demonstrate efficacy. Clinical trials of psychiatric treatments are dependent on disease models grounded in the descriptive psychiatry of the 1960s and 1970s. Major pharmaceutical companies have stopped financing efforts to discover new drugs for psychiatric disorders. New ideas are needed, and genome-scale genetic analyses for psychiatry might come to the rescue. It is necessary to discover the biochemical pathways involved in disease pathogenesis in order to deduce what functions to target for therapeutics discovery. Emerging results from genome-scale genetic studies of schizophrenia and autism appear to suggest certain areas of neural function as possible sources of disease risk. See: Hyman SE. Revolution stalled. Sci Transl Med. 2012 Oct 10;4(155). PMID 23052291
Studies in the field of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and ventilator-induced lung injury (VILI) have creatively applied and integrated genomics, bioinformatics and/or proteomics to identify novel candidate molecular targets. Concepts are being explored, including the role of the coagulation cascade, the renin-angiotensin system, and the synergism of signaling pathways involved in mechanical and biomolecular injury. It is clear that ALI/ARDS and VILI involve the interaction of a complex network of cellular components. Genetic predisposition contributes to disease susceptibility and severity in ALI/ARDS, where the outcome of patients with similar clinical characteristics can be dramatically different. As technological developments in genomics, proteomics, and bioinformatics continue, significant collaborative efforts to expand the size, scope and integrative approaches to critical illness will be necessary in order to achieve the goal of developing molecular strategies to modulate, regulate and reverse the process of injury. See: PMID 18195619
Beginning in the 1980s, Brookhaven National Laboratory started to develop a “dual-purpose” radionuclide using tin-117m, with emissions suitable for both imaging and therapy. The intent was to create a theragnostic radionuclide to perform tailored low-dose molecular imaging, followed by performing higher-dose targeted molecular therapy in the same patient. A major problem they continue to address is the lack of availability, in sufficient quantities, of a majority of the best candidate theragnostic radionuclides. They recently developed 5 theragnostic radionuclide/radionuclide pair items, whose nuclear, physical, and chemical characteristics seem to show great promise for personalized cancer and other therapies. See: PMID 22475424
The field of perioperative genomics continues to develop. It appears that the host response to surgery and trauma is at least in part genetically determined. The precise way in which genetic variation affects outcomes after injury and surgical treatment remains unknown. Genome-wide association studies have not been able to explain individual response to surgery. Attention has been turned to deep resequencing of candidate genes to explore the perioptome – the space where the genome, the operating room, and the ICU intersect. See: PMID 20543686
Vascular rejection of allografts requires Translational Medicine (TM) to develop different immunosuppressive strategies that can protect graft vessels and parenchyma. Additional opportunities for TM to advance molecular discoveries to clinical use in surgery include approaches for the diagnosis and inhibition of tissue ischemia before irreversible changes occur, and alternative approaches to reducing vascular rejection such as the induction of host immune tolerance to the allograft or cytoprotective strategies to prevent vessels from injury. See: PMID 11689456 ~ Free full text article
A wide array of molecular markers may be used in the near future as adjuncts to currently established prognostic parameters in urologic malignancies. Many potential new targets of therapy are under investigation, with markers being developed for the analysis and targeted treatment of bladder cancer, prostate adenocarcinoma, and renal cell carcinomas. See: PMID 22458900 ~ Free full text article