A gene is the basic unit of heredity. Genes act as instructions to make molecules called proteins. The Human Genome Project has estimated that every human has between 20,000 and 25,000 genes.
New knowledge about the role of genes in health and disease holds the promise of developing safer, more effective treatments for many diseases. VA researchers are at the forefront of this effort.
VA is well-equipped to study genomics, which is the use of peoples' individual genetic profiles to customize their health care. The department has a large and diverse patient population; an integrated network of basic research and clinical applications; and an electronic medical record system that offers a rich source of health and clinical data.
Among the areas in which VA already uses genomics-based approaches to provide care are tests to confirm hemochromatosis, a hereditary condition in which iron builds up in the body. VA also uses genomic medicine to predict Veterans' responses to cholesterol-lowering statin drugs and to help diagnose breast, colon, and other cancers.
Genomic medicine has the potential to launch the world into a new era of customized medical care. Researchers hope to eventually provide treatments that are as individualized as diseases are, and to provide health information to patients that will allow them even more control over their own care.
The Human Genome Project (HGP) was an international research effort to sequence and map all of the genes, which are together known as the genome, of humans. When the HGP was completed in April 2003, its results gave scientists the ability, for the first time, to read nature's complete genetic blueprint for building a human being.
With the completion of the HGP, scientists now have a detailed map of humans' genetic structure. VA researchers are focused on translating this knowledge into improved medical care that is customized to a patient's specific genetic profile.
The completion of the genome map has created the emerging field of "personalized medicine," and the availability of increasingly detailed genomic information, which will allow health care providers to better optimize therapies for each individual patient in the future.
The next step in genomics research is to learn which genetic variations, or DNA changes, are associated with a particular disease, condition, or health characteristic. To do this, researchers must analyze and compare DNA from a huge number of people—some with the disease or condition, others without.
New discoveries in genomics, accelerated by the Million Veterans Program (see below), as well as by advanced robotics, super-computers and other automated systems for information analysis, will improve screening and diagnosis and lead to more effective treatments.
VA's Million Veteran Program (MVP) was conceived and implemented to foster genomic discoveries and to bring personalized medicine to the forefront of VA health care.
MVP's aim is to build one of the world's largest databases of genetic, military exposure, lifestyle, and health information. VA researchers are partnering with Veterans receiving their care from the Veterans Health Administration (VHA) to study how genes affect health.
VA is seeking blood samples from one million Veterans throughout the nation. The blood samples, which contain DNA material, will be stored anonymously for future research.
Veterans who volunteer to be part of the program are asked to fill out surveys about their health and health-related behaviors, and to complete an optional health assessment. They are also asked permission to allow VA researchers to confidentially access information from their medical records, and to allow VA researchers to contact them in the future.
The program has extensive safeguards in place to ensure that information security and patient confidentiality are top priorities. As of early March 2014, more than 250,000 Veterans had enrolled in MVP.
Among recent discoveries by VA researchers was a finding that genetic variations associated with a protein called macrophage migration inhibitory factor may signal an increased risk for prostate cancer recurrence. Another VA group found that while one variant of the "bc12" gene is generally associated with longer survival in patients with kidney cancer, another variant of the gene may actually predict worse outcomes.
Two VA researchers at the Kansas City Medical Center recently learned that a gene called CCN5/WISP-2 significantly suppresses the invasive characters of aggressive breast cancer cells.
CCN5, the researchers believe, is a micromanager of cells in the breast, telling cells what their proper function is in the body and how that function should be accomplished. Its absence allows such cells to transform themselves, sometimes into malignant cancer cells.
VA Palo Alto researchers , along with researchers from the Stanford University School of Medicine, tested 144 middle aged and older airplane pilots on flight simulators three times over two years. They found that having one version of a gene that codes for a certain protein (brain-derived neurotropic function, or BDNF), as opposed to the other, doubled the rate of decline in performance over the two-year period.
The variation implicated in the study has been previously linked to other psychiatric disorders, including depression, stroke, anorexia nervosa, anxiety-related disorders, suicidal behavior, and schizophrenia.
A current VA study is looking at which genes may contribute to the risk of amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease. DNA from Veterans with ALS who agreed to be part of a registry is being compared with DNA from patients without the disease.
VA researchers are also looking at other possible triggers for ALS, such as family and medical history, diet, medications, and exposure to toxins. This is the first study of its kind to look at the interaction of genes and environment in susceptibility to ALS.
Another study, which aims to identify genes associated with chronic and debilitating mental health disorders, stands to be one of the largest studies of its kind. In addition to identifying genes associated with these conditions, genetic studies in this area aim to help researchers find new treatments and treat people before their diseases become more severe.
Other VA researchers are working to identify genes that affect a person's response to the experience of deployment, especially combat exposure. By conducting careful assessments in Veterans affected by combat-related PTSD and with their consent, analyzing their DNA samples, researchers hope to pinpoint genetic variants that contribute to PTSD and other post-deployment adjustment disorders, such as depression. This may result in more effective treatments, and perhaps even preventive measures.
Finally, a new study is examining clinical effectiveness of the delivery of targeted genomic-based therapy in the management of Veterans with advanced lung cancer. The researchers are also measuring knowledge, facilitators, and barriers to delivering such therapy for Veterans. This information will help decision-makers, clinicians, and patients in choosing the type of therapy that will provide optimal care.
As in all VA research efforts, protection of Veterans' information is the highest priority in genomic medicine research. Various safeguards have been established to protect Veterans' privacy and safeguard the confidentiality of their genetic information, including strict rules for collection of DNA samples for VA research studies.
To maintain privacy, Veterans' samples are labeled and stored with a code that does not contain any personal information (such as name, address, or Social Security number). Researchers who are granted access to Veterans' samples for analysis are not given any information that would identify a specific Veteran.
A "key" that links the code to the Veteran's identity is maintained in an encrypted file that only a limited number of authorized staff can access.
A Genomic Medicine Program Advisory Committee, which advises the Secretary of Veterans Affairs, lays the groundwork for the VA Research Genomic Medicine Program. Members include leaders in the public and private sectors and academia in the fields of genetic research and medical genetics; genomic technology; health information technology; and health care delivery, policy, and program administration. The committee also includes a Veterans Service Organization representative.
Video: Genomics Research
Video: Genetics Research at VA
Gene may alter women's PTSD risk, VA Research Currents, Winter 2013-14
MVP: Veterans share their reasons for enrolling, VA Research Currents, Fall 2013
Press release: The Million Veteran Program: VA's Genomics Game-Changer Launches Nationwide. VA press release, May 5, 2011
Delivery of genomic medicine for common chronic adult diseases: a systematic review, Scheuner MT, Sieverding P, Shekelle PG. Many gaps in knowledge about organization, clinician, and patient needs must be filled to translate basic and clinical science advances in genomics of common chronic diseases into practice. JAMA, 2008 Mar 19;299(11):1320-34.
Veterans' attitudes regarding a database for genomic research . Kaufman D, Murphy J, Erby L, Hudson K, Scott J. Majorities of Veterans Affairs health patients in a broad range of demographic groups supported the establishment of a genomic database and showed willingness to participate. Genet Med, 2009 May;11(5):329-37.
CCN5/WISP-2: A micromanager of breast cancer progression, Banerjee SK, Banerjee S. Loss of CCN5 activity may promote breast cancer progression; application of CCN5 protein may represent a novel therapeutic intervention in breast cancer and possibly pancreatic cancer. J Cell Commun Signal, 2012 Jun;6(2):63-71.
Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung . Wang J, Qian J, Hoeksema MD, Zou Y, Espinosa AV, Rahman SM, Zhang B, Massion PP. Three genes provide novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of lung cancer. Clin Cancer Res. 2013 Oct 15;19(20):5580-90.
A cancer genetics toolkit improves access to genetic services through documentation and use of the family history by primary-care clinicians . Scheuner MT, Hamilton AB, Peredo J, Sale TJ, Austin C, Gilman SC, Mowen MS, Goldzweig CL, Lee M, Mittman BS, Yano EM. A multicomponent approach to the systematic collection and use of family history by primary-care clinicians increased access to genetic services. Genet Med 2014 Jan;16(1):60-9.
The VA Hypertension Primary Care Longitudinal Cohort: Electronic medical records in the post-genomic era . Salem RM, Pandey B, Richard E, Fung MM, Garcia EP, Brophy VH, Schork NJ, O'Connor DT, Bhatnegar V. The coupling of detailed medical databases with genetic information has the potential to facilitate the genetic study of hypertension and other complex diseases. Health Informatics J, 2010 Dec;16(4):274-86.
Preferences regarding genetic research results: comparing veterans and nonveterans responses. Arar N, Seo J, Lee S, Abboud HE, Copeland LA, Noel P, Parchman M. Participants believed they would prefer receiving their genetic research results. Veterans are similar to non-veterans in their preferences. Public Health Genomics 2010;13(7-8);431-9.
With enrollment at 200K, VA's Million Veteran Program inks contracts for genetic analysis, Genomeweb, Nov. 13, 2013.
Houston VA enrolls 8,000 in Million Veteran Program, Examiner, May 7, 2013
VA's genomic and EHR database aims to drive personalized care, Government Health IT, Nov. 21, 2012
The Million Veteran Program: Building VA's Mega-Database for Genomic Medicine, Health Affairs Blog, Nov. 19, 2012.
Veterans to create world's largest medical database, National Public Radio, Nov. 14, 2011.
Genomic medicine program advisory committee, Department of Veterans Affairs
MAVERIC (Massachusetts Veterans Epidemiology Research and Information Center), U.S. Department of Veterans Affairs
National Human Genome Research Institute, National Institutes of Health
Public Health Genomics, Centers for Disease Control and Prevention
genomics.energy.gov, U.S. Department of Energy
Drugs: Genomics, U.S. Food and Drug Administration