Office of Research & Development

VA research on

Genomics


Introduction

Heredity is transmitted from your parents through DNA. A gene is a region of DNA that contains instructions to make RNA molecules that code for other proteins. When genes are transmitted through the process of reproduction, they govern inheritance of genetic traits like hair color or blood type.

The Human Genome Project (HGP) was an international research effort to sequence and map all human genes, which are together known as the genome. The HGP's completion in 2003 gave scientists the ability, for the first time, to read nature's complete genetic blueprint for the human organism.

HGP has estimated that every human has between 20,000 and 25,000 genes, and as we know more, these numbers continue to change. Genomic medicine is the application of our rapidly expanding knowledge of the human genome to medical practice. VA uses genomic medical research to find new health care solutions and move those into Veterans' care.

New knowledge about the role of genes in health and disease holds the promise of developing safer, more effective, personalized treatments for many conditions. The completion of the genome map has created the emerging field of "precision medicine" (also known as "personalized medicine"), which allows health care providers to better optimize therapies for each individual patient. One major area that precision medicine has had a major effect on is in the treatment of certain cancers, especially those found in the lung, colon, and blood.

VA is well-equipped to study genomics. The department has a large and diverse patient population; an integrated network of basic research and clinical programs; and an electronic medical record system that offers a rich source of health and clinical data.

One of the areas in which VA already uses a genomics-based approach to provide care for Veterans is testing to confirm hemochromatosis, a hereditary condition in which iron builds up in the body. VA physicians also use genomic medicine to predict Veterans' responses to cholesterol-lowering statin drugs and to help diagnose and treat breast, colon, lung, and other cancers. VA researchers hope to eventually use genetic information to determine the right type and dosage of antidepressant medication and other drugs for individual patients.

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Selected Major Accomplishments in VA Research

  • 2006: Launched a genomic medicine initiative to advance knowledge of how genes affect health and to promote personalized medicine for Veterans
  • 2007: Established a laboratory in Little Rock, Arkansas, to conduct diagnostic or treatment-related genetic tests for Veterans
  • 2011: Launched the Million Veteran Program (MVP) to establish one of the world's largest databases of health and genetic information
  • 2014: Found that an alteration in a common gene could help predict how well patients with lung cancer respond to chemotherapy
  • 2016:
    • Developed a test to determine whether a respiratory illness is caused by an infection from a virus or bacteria
    • Announced a collaboration with the Department of Energy (DoE) to apply the powerful computing assets available at DoE National Labs to the MVP program
    • Began the APOLLO Network, a new tri-agency coalition with the Department of Defense and the National Cancer Institute that will enable oncologists to more rapidly and accurately identify effective drugs to treat cancer based on their patients' unique genomic profiles
    • Announced a collaboration with IBM to expand and scale access to precision medicine for Veterans with cancer
  • 2018: Found that a risk score can identify people with a precursor to Alzheimer's disease who are still in their 50s

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New, Ongoing, and Published Research

Genomic medicine has the potential to launch the world into a new era of personalized medical care. VA researchers are working to developed personalized treatments based on patients' genes and other individual factors.

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.

➤ Genomic medicine implementation

Genomic medicine implementation is focused on the improvement of Veterans' health through genomics and is focused on developing processes and methodologies that enable genomic research-to-practice tests to become sufficiently validated and ultimately implemented within routine care settings.

This includes the assessment of current research within the Office of Research and Development, as well as development of novel approaches to evaluate and implement genomic testing in health care. One such large-scale effort is PRIME Care (Precision Medicine in Mental Health Care) performing genomic drug metabolism testing (pharmacogenomics) to help reduce adverse events in patients medically treated for major depression. It may also include leveraging and analyzing large-scale data maintained within VA's Million Veterans Program (MVP-see below) and other sources; the clinical validity and utility of genomic tests in clinical care settings; and implementing the return of genomic test results in routine care, taking into account health system, provider, and patient factors associated with clinical deployment and spread.

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➤ Million Veteran Program

MVP was conceived and implemented to foster genomic discoveries and to bring precision 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. Through MVP, VA researchers are partnering with Veterans to study how genes affect health.

MVP is well more than halfway past its enrollment goal of 1 million Veterans, whose DNA samples and health information will provide an unprecedented resource for researchers. DNA, or deoxyribonucleic acid, is a heritable material present in nearly all living organisms. It is the carrier of genetic information.

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 participant confidentiality are top priorities. As of August 2018, more than 690,000 Veterans have enrolled in MVP, and the program is on target to reach its goal of 1 million enrolled Veterans by 2021. The program is expected to reach its goal of having information about participants' DNA (or genes) and environment and health data from 1 million Veterans in the next few years. (To receive the program's quarterly newsletter, MVP Insider, click here.)

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➤ Genomics and mental health

Precision medicine in depression—To achieve a remission from depression, patients and their health care providers must be persistent and try multiple treatments until they find one that is both tolerable and effective. Pharmacogenic testing is a type of genetic testing meant to predict a patient's likelihood of experiencing an adverse event from a given drug, or to not respond to that drug. In the last several years, such testing has become widespread for patients with depression as a means of implementing "precision medicine" (the tailoring of medical treatment to the individual characteristics of each patient).

Researchers with VA's Center for Health Equity Research and Promotion (CHERP) in Philadelphia are looking at the usefulness of pharmacogenic testing in treating major depressive disorder with or without concurrent PTSD. Patients and providers in the study will either be given the results of such testing immediately or after six months of treatment as usual. The study is scheduled to be completed in 2022.

Genetic markers predict lithium nonresponseLithium is the standard mood stabilizer used to treat bipolar disorder, but up to 30 percent of patients do not respond to the drug. In a study published in 2018, an international consortium, including several VA researchers, looked at the genomes of more than 2,000 patients with bipolar disorder. They found that most patients who had gene variations previously shown to predict schizophrenia also did not respond to lithium. The results can be used to predict how effective lithium treatment will be for individual patients.

Genetic risk factors for PTSD—A large international study involving several VA researchers examining genetic risk factors for posttraumatic stress disorder (PTSD) was published in 2018. The study included some 200 billion pieces of genetic information from more than 20,000 adults throughout the world. The results demonstrate genetic influences on the development of PTSD, identify shared genetic risks between PTSD and other psychiatric disorders, and highlight the importance of multiethnic and multiracial samples.

According to the researchers, even larger samples are needed to home in on the specific genes that may be linked to the disorder.

Sleep problems may be genetic and lead to psychiatric disorders—As many as 20 percent of Americans and 50 percent of Veterans have trouble sleeping. In 2018, a team led by researchers with the VA San Diego Healthcare System and the University of California, San Diego, published a study identifying specific variants on chromosomes that may trigger the development of sleep problems and demonstrating a genetic link between insomnia and psychiatric disorders such as depression and physical conditions such as type 2 diabetes.

The team analyzed data from more than 33,000 soldiers participating in the Army Study to Assess Risk and Resilience in Servicemembers. They confirmed that insomnia has a partially heritable basis and also found a strong genetic link between insomnia and type 2 diabetes. Among participants of European descent, the team also found a genetic tie between sleeplessness and major depression.

SKA2 gene may predict PTSD risk—Biomarkers are measurable indicators of health and disease. A 2016 study by researchers at VA's National Center for PTSD, the VA Boston Healthcare System, and the Boston University Healthcare System identified a gene, SKA2, that can potentially be used as a biomarker to help predict, before deployments, which service members may be more at risk to develop severe PTSD as the result of a high lifetime burden of stress and subsequent combat exposures.

The research team performed magnetic resonance imaging brain scans and examined blood samples from 200 Iraq and Afghanistan Veterans whose health information is part of a database maintained by VA's Translational Research Center for TBI and Stress Disorders.

They found a chemical change, called methylation, had switched off the function of the SKA2 gene in some of those Veterans. This change in brain chemistry was correlated with decreases in the thickness of the prefrontal cortex, and with greater PTSD severity.

The team emphasizes more research is needed to better understand the associations they observed between SKA2 status, cortical thickness, and PTSD severity. Nonetheless, they suggest that in the future it may be possible to use genetic blood tests to help assess the susceptibility of service members for combat-related PTSD.

Predicting response to SSRIs—Brain scans of Veterans with PTSD have led researchers to an area of the prefrontal cortex that appears to be a good predictor of how well Veterans who receive treatment with SSRIs will respond to that treatment.

The prefrontal cortex is the part of the brain responsible for emotions and mood regulation. Paroxetine (sold as Paxil) and sertraline (Zoloft) are among the SSRI class of antidepressants and are currently the only drugs approved by the Food and Drug Administration to treat PTSD. Fluoxetine (Prozac) is another SSRI, but it has not yet been approved to treat PTSD.

The 2016 study, led by investigators from the Jesse Brown VA Medical Center and the University of Illinois at Chicago, found that patients who showed the most improvement from receiving SSRIs were those who showed the least activation of a brain area called the right ventrolateral prefrontal cortex before their treatment—even though that area of the brain was not the exact area that appeared to be affected by the treatment.

Traumatic brain injury and PTSD—In 2015, researchers at the James J. Peters VA Medical Center in the Bronx and VA's War-Related Illness and Injury Study Center in East Orange, New Jersey, learned that four specific RNA molecules, known by the designations ACA48, U35, U55, and U83A, were found at significantly lower than normal levels in Veterans who had had traumatic brain injuries (TBIs) and also suffered from posttraumatic stress disorder (PTSD).

RNA, or ribonucleic acid, is a nucleic acid present in all living cells. Its principal role is to act as a messenger carrying instructions from DNA for controlling the synthesis of proteins.

The researchers tested blood samples from 58 Iraq and Afghanistan Veterans. Some of the Veterans had a combination of TBI and PTSD, some had only one of the illnesses, and others had neither problem.

Veterans who had only PTSD had significantly lower levels of only the U55 RNA module, and Veterans who only had a TBI and not PTSD had normal levels of all four modules.

The team hopes that their study will eventually result in a simple blood test to help diagnose the two issues in Veterans.

Biomarkers of suicide—VA researchers at the Durham VA Medical Center and the Mid-Atlantic MIRECC found, in a study published in 2014, that changes in the levels of certain amino acids in the body may contribute to suicide risk. The amino acids in question are important in regulating people's mood and behavior, although understanding their exact relationships to suicide will require further study.

In 2016, VA researchers at the Rocky Mountain MIRECC for Suicide Prevention in Denver, along with researchers in three other countries, found reduced activity in the enzyme ACMSD in some people who have tried to kill themselves.

The enzyme is part of a chain of biochemical reactions called the kynurenine pathway, which is activated by inflammation. When it behaves sluggishly, it causes abnormal levels of two acids in the body, which could be measured in blood tests to help identify patients of high risk of suicide.

In 2017, a team led by a researcher from the San Diego VA Healthcare System identified a gene variation that may be linked to increased risk of suicide attempts. The researchers studied the mapped genomes of a large group of soldiers to look for similarities in those who had attempted suicide. They found similar variations in two genes (CEP162 and MRAP2) in one genome location. This gene variation may increase the risk of suicide and may also show a genetic link between the risk of suicide and bipolar disorder.

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➤ Genomics and neurodegenerative disease

A polygenic risk score can identify Alzheimer's disease risk in younger populations— Polygenic risk scores summarize genome-wide genotype data into a single variable that predicts disease risk. A team led by a researcher from the VA Boston Healthcare Systemfound, in 2018, that an Alzheimer's disease polygenic risk score can be used to correctly identify adults with mild cognitive impairment (MCI) who were only in their 50s. Previously, polygenic risk scores were only used to predict the likelihood of Alzheimer's for people in their 70s. Current evidence indicates that MCI often, but not always, arises from a lesser degree of the same types of brain changes seen in Alzheimer's disease or other forms of dementia. Doctors currently diagnose MCI based on observed behavioral criteria.

According to the team, the AD pathological process begins decades before the onset of dementia. By focusing on a younger population with cognitive improvement, researchers may be better able to identify patients for critical early interventions and clinical trials.

Hippocampus size and memory—The hippocampus is a small region of the brain that plays an important role in memory and spatial navigation. VA researchers and others have shown that the smaller a person's hippocampus is, the greater the chances of cognitive decline and Alzheimer's disease late in life.

In 2014, a team of researchers from VA's Geriatric Research, Education, and Clinical Center in Nashville and Vanderbilt and Duke universities found that variants in a gene responsible for regulating blood pressure may also cause shrinking of the hippocampus.

The team found that three variants of the AGTR1 gene, part of a hormone system responsible for regulating blood pressure and fluid balance, were associated with greater change in hippocampal volume and memory problems. This shrinkage occurred only in the right side of the hippocampus, which is related more to navigation.

The study looked at gene variants in 138 adults older than age 60. The team hopes that the gene variant can serve as a biomarker for future risk of memory loss and depression, and possibly for other psychiatric illnesses. It may also provide clues to guide future treatments.

Genomics and Parkinson's disease—Researchers with the VA Pittsburgh Healthcare System and the University of Pittsburgh School of Medicine found, in 2015, that gene therapy to reduce the production of a brain protein could successfully prevent the development of Parkinson's disease (PD) in rats.

PD is a chronic neurological disease that is commonly referred to as a movement disorder.

The disease can cause muscle rigidity, delayed movement, poor balance, and tremors. PD is caused by aggregates or deposits of a protein called alpha-synuclein within neurons. It is also linked to a dysfunction of mitochondria, the powerhouses of the cell that produce energy for the body.

According to the research team, their study was the first to show that mitochondria and alpha-synuclein can interact in a damaging way in vulnerable cells, and that targeting alpha-synuclein might be an effective way to treat the disease.

In their study, the team blocked the expression of alpha-synuclein in rats' brains by injecting the rats with a harmless virus called AAV2. They then exposed the rats to a naturally occurring pesticide called rotenone, which creates Parkinson-like body chemistry changes in rats exposed to it.

They found that their gene therapy protected the rats from the effects of rotenone, and concluded that gene therapy aimed at reducing alpha-synuclein production has a protective effect and successfully prevented the development of PD in a rat model.

The team is now working to identify the pathways by which alpha-synuclein affects the mitochondrial function and to develop potential drug therapies that target this mechanism.

Partial MHC molecules may be an effective multiple sclerosis treatment—MHC molecules are important in initiating immune responses in the body. In mice and related rodents, experimental autoimmune encephalomyelitis (EAE) is a similar illness to MS. In a 2017 study, VA researchers found administering partial MHC (pMHC) molecular constructs to rodents not only reduced the severity of the disease but also markedly reduced demyelination and damage to axons in the central nervous system. They also found that the effective dose of those constructs is sex-dependent and might be regulated by estrogen signaling.

Cytokines found in progressive MS identified—Researchers with the VA Portland Health Care System, the Oregon Health and Science University, Yale University, and the University of California, San Francisco, published a paper in 2017 in which they identified two related cytokines and associated genetic markers that may explain why some people develop MS. (Cytokines are small, specific proteins released by cells that have a specific effect on the interactions and communications between cells.)

The two cytokines, macrophage migration inhibitory factor (MIF) and D-dopachrome tautomerase (D-DT), can worsen MS by increasing inflammation within the central nervous system. The research team also identified two genetic markers that enhance the expression of both cytokines that occurred more frequently in MS patients with the progressive form of the disease, suggesting that a simple genetic test could be used to identify patients at risk of developing this form of MS.

The finding may open the door to the use of precision medicine to prevent and treat the progressive form of the disease.

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➤ Genomics and cancer

APOLLO network launched—In 2016, VA announceda partnership with DoD and the National Cancer Institute (NCI) to tailor cancer care for patients based on the genes and proteins associated with their tumors. The tri-agency program created the nation's first system in which cancer patients' tumors are routinely screened for gene and protein information, with the goal of finding targeted therapies for each individual patient. The process will also generate new information to improve clinicians' ability to treat the disease. The program is called the Applied Proteogenomics Organizational Learning and Outcomes Consortium (APOLLO).

VA, IBM Develop Public-Private Partnership—Also in 2016, VA and IBM Watson Health announced a public-private partnership to help doctors expand and scale access to precision medicine for 10,000 Veterans with cancer. IBM's Watson for Genomics technology is providing information to help VA physicians identify precision treatment options for almost 30 times more patients than could be previously served.

The collaboration is speeding up the ability of VA physicians to help identify precision treatment options for Veterans. Scientists and pathologists sequence DNA for Veterans with cancer, then feed de-identified genetic alteration files into Watson. Watson generates a report for physicians that identifies the likely cancer-causing mutations and possible treatment options to target those specific mutations through a comprehensive review of existing medical literature.

New polygenic hazard score can predict prostate cancer—A large research team including VA researchers has developed and validated a genetic tool using polygenic hazard scores to predict the age at which men may develop aggressive prostate cancer, a disease that kills more than 26,000 American men every year. The tool, which is more precise than the existing prostate-specific antigen (PSA) test, may potentially be used to help guide decisions about who to screen for prostate cancer and at what age. A study describing the tool was published in 2018.

Prostate cancer gene more active in African-American men—A 2016 study by a research team from the Michael E. DeBakey VA Medical Center in Houston, Baylor College of Medicine, and research organizations in China and India identified a gene that can cause cancer that is more active in African-American men with prostate cancer than in European-American men with prostate cancer. The finding suggests that genetic factors can contribute, at least in part, to the higher incidence of prostate cancer among African-American men compared with men of other ethnic groups.

Effect of microRNAs on bladder cancer—In 2015, researchers at the VA Northern California Health Care System and the University of California, Davis, found that microRNAs (small RNA modules that help regulate genes in the body) could help suppress cancer cells in the bladder.

The team found that in cancer cells in the bladder, there tended to be a shortage of the microRNA module miR-148a. This module can be reproduced in laboratories, raising the possibility that if it can be introduced into cancer cells in a targeted way, it can help suppress the growth of those cells.

Bladder cancer is the fourth most common cancer in men, and the ninth most common in women.

Two RNA molecules may suppress tumor growth—Another study of RNA, this one published in 2016 by researchers at the VA Palo Alto Healthcare System and Stanford University School of Medicine, found that two RNA molecules, SNORD50A and SNORD50B, are missing in 10 to 40 percent of tumors in patients with 12 common cancers—and that patients whose tumors do not have these molecules have poorer survival rates than their peers.

The two molecules directly inhibit a well-known cancer-associated protein called K-Ras. In the absence of those molecules, K-Ras becomes hyperactive and emits continued signals to cancer cells to divide.

According to the research team, this is the first time an RNA molecule of this kind has been shown to act as a powerful tumor suppressor. K-ras mutation is an essential step in the development of nearly all human cancers. Understanding how the two molecules block the ability of K-Ras to be activated may open new doors to blocking its function in cancer.

Precision Oncology Program goes nationwide—A pilot that began in 2015 in VA's New England Healthcare System is now rolled out across all VA facilities that treat patients with advanced cancers. POP's goal is to double the survival of patients with advanced non-small cell lung cancer.

Under the program, when Veterans are diagnosed with non-small cell lung cancer, VA physicians take a specimen of their tumor and send it to qualified laboratories for targeted genomic sequencing, a process that determines the DNA sequence of genes that are considered important in lung cancer.

The sequencing identifies specific mutations, or changes, that are causing the lung cancer to grow, allowing Veterans to benefit from drugs that are targeted to those mutations, and to take part in clinical trials of new drugs targeted toward their specific mutations.

As of June 2016, 18 facilities are enrolled in POP, with more beginning the process. More than 300 tumor samples have been sent for testing. As a result, multiple patients have received targeted agents specifically designed to treat their tumors based on genetic testing. VA is partnering with other government agencies, non-profit organizations, and industry to expand access to novel treatment therapies.

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➤ Genomics and respiratory ailments

How COPD survives in human airwaysAs part of a 15-year study of chronic obstructive pulmonary disease (COPD), researchers at the VA Western New York Healthcare System, the University of Buffalo, Yale University, and the University of Maryland have identified genetic changes to a pathogen, nontypeable Haemophilus Influenzae, which allow it to survive in human airways, including the nose, nasal cavities, the mouth, larynx, trachea, and bronchial pathways. The pathogen is the source of much of the misery COPD patients endure in breathing.

The genetic changes identified in the 2018 study are key to determining where the pathogen's vulnerabilities are and what the best strategy might be to eradicate it. According to the team's lead researcher, the ability to effectively sequence the pathogen's genome and analyze it was critical to the researchers' success.

Finding the causes of respiratory illnessResearchers at the Durham VA Medical Center, Johns Hopkins University, and Duke University are now fine-tuning a test that can determine whether a respiratory illness is caused by an infection from a virus or bacteria.

The team has identified gene signatures that reflect which of a patient's genes are turned on or off, to indicate the cause of an infection. These gene signatures can be derived from a small blood sample.

The signatures were tested in a study, published in 2016, and were found to be 87 percent effective in classifying more than 300 patients with flu viruses, rhinovirus, several strep bacteria, and other common infections. The signatures also indicated when no infection was present.

The team hopes to develop a blood test that can be used in clinics to distinguish between bacterial and viral infections in an hour or less (the current test takes about 10 hours to evaluate), and to guide appropriate treatment. Such a test should reduce excess use of antibiotics, which is a risk to both the patient and to public health.

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➤ Genomics and arthritis

In 2017, researchers at the VA Tennessee Valley Healthcare System found that small segments of RNA are altered in people with rheumatoid arthritis. The researchers looked at the RNA variations in blood plasma of people with rheumatoid arthritis and found significant alterations in 12 RNA sequences compared to subjects without arthritis. The results could be used to help diagnose the disease.

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➤ Genomic pain treatments

Inherited erythromelalgia is a severe pain syndrome that occurs when genetic mutations cause the body's pain-sensing system to go into high gear, leading to flare-ups of pain and burning sensation in response to seemingly benign triggers like warm temperature and mild exercise.

In a study published in 2016, a team of researchers with the VA Connecticut Healthcare System and Yale University successfully tailored a personalized treatment approach to the syndrome, using molecular modeling and other techniques to find the most effective drug treatment plan for two patients from the same family. The search, which found that the drug carbamazepine was the most effective treatment, was guided by the exact location of a mutation in each patient's genome.

According to the researchers, the study demonstrated that it is possible to use genomics and molecular modeling to guide pain treatment.

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More on Our Website

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Selected Scientific Articles by Our Researchers

Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Pettigrew MM, Ahern CP, Gent JF, Kong Y, Gallo MC, Munro JB, D'Mello A, Sethi S, Tettelin H, Murphy TF. An advance to our understanding of how nontypeable Haemophilus influenza, a bacterial pathogen that plays a critical role in COPD, adapts to survival in the human respiratory tract. Proc Natl Acad Sci USA. 2018 Mar 19. (Epub ahead of print.)

Genome-wide analysis of insomnia disorder. Stein MB, McCarthy MJ, Chen Cy, Jain S, Gelertner J, He F, Heringa SG, Kessler RC, Nock MD, Ripke S, Sun X, Wynn GH, Smoller JW. Ursano RJ. Insomnia-associated genes may contribute to the genetic risk underlying a range of health conditions including psychiatric disorders and metabolic disease. Mol Psychiatry. 2018 Mar 8. (Epub ahead of print.)

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability. Duncan LE et al. Results demonstrate genetic influence on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders, and highlight the importance of multiethnic and multiracial samples. Mol Psychiatry. 2018 Mar;23(3):666-673.

Use of an Alzheimer's disease polygenic risk score to identify mild cognitive impairment in adults in their 50s. Logue MW, Panizzon MS, Elman JA, Gillespie NA, Hatton SN, Gustavson DE, Andreassen OA, Dale AM, Franz CE, Lyons MJ, Neale MC, Reynolds CA, Tu X, Kremen WS. An Alzheimer's disease polygenic risk score can identify mild congnitive impairment in adults who were only in their 50s. Mol Psychiatry. 2018 Feb 27. (Epub ahead of print.)

Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts. Seibert TM et al. Polygenic hazard scores can be used for personalized genetic risk estimates that can predict for age at onset of aggressive prostate cancer. BMJ. 2018 Jan 10;360:j5757.

Association of polygenic score for schizophrenia and HLA antigen and inflammation genes with response to lithium in bipolar affective disorder: a genome-wide association study. International Consortium on Lithium Genetics et al. There is a negative association between high genetic loading for schizophrenia and poor response to lithium in patients with bipolar affective disorder. JAMA Psychiatry. 2018 Jan 1;75(1):65-74.

Genomewide association studies of suicide attempts in US soldiers. Stein MB et al. MRAP2, a gene expressed in the brain and adrenal cortex and involved in neural control of energy homeostasis is a plausible susceptibility gene for suicidality that should be further studied. Am J Med Genet B Neuropsychiatr Genet. 2017 Dec;174(8):786-797.

MIF and D-DT are potential disease severity modifiers in male MS subjects. Benedek G, Meza-Romero R, Jordan K, Zhang Y, Nguyen H, Kent G, Li J, Siu E, Frazer J, Piecychna M, Du X, Sreih A, Leng L, Wiedrick J, Caillier SJ, Offner H, Oksenberg JR, Yadav V, Bourdette D, Bucala R, Vandenbark AA. Two related cytokines and associated genetic markers may explain why some people develop MS. Proc Natl Acad Sci USA. 2017 Oct 3;114(40):E8421-E8429.

Rapid evidence review of the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment versus usual care for major depressive disorder. Peterson K, Dieperink E, Anderson J, Boundy E, Ferguson L, Helfand M. Certain pharmacogenomics tools show promise of improving short-term remission rates of women in their mid-40s with few comorbidities. Important evidence limitations preclude recommending their widespread use and indicate a need for further research. Psychopharmacology (Berl). 2017 Jun;234(11):1649-1661.

Sex-dependent treatment of chronic EAE with partial MHC class II constructs. Benedek G, Chaudhary P, Meza-Romero R, Calkins E, Kent G, Offner H, Bourdette D, Vandenbark AA. Male and female mice can be effectively treated for EAE, a disease similar to MS in humans, with different doses of pMHC. J Neuroinflammation. 2017 May 6;14(1):100.

MNX1 is oncogenically upregulated in African-American prostate cancer. Zhang L, Wang J, Wang Y, Zhang Y, Castro P, Shao L, Sreekumar A, Putluri N, Guha N, Deepak S, Padmanaban A, Creighton CJ, Ittmann M. MNX1 is a novel targetable oncogene increased in African-American prostate cancer that is associated with aggressive disease. Cancer Res. 2016 Nov 1; 76(21):6290-6298.

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation. Brundin L, Seligren CM, Lim CK, Grit J, Palsson E, Landen M, Samuelsson M, Lundgren K, Brundin P, Fuchs D, Postolache TT, Traskman-Bendz L, Guellemin GJ, Erhardt S. Measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and the enzyme ACMSD is a potential therapeutic target in suicidal behavior. Transi Psychiatry. 2016 Aug 2;6(8):e865.

Pharmacology for pain in a family with inherited erythromelagia guided by genomic analysis and functional profiling. Geha P, Yang Y, Estacion M, Schulman BR, Tokuno H, Apkarian AV, Dib-Hall SD, Waxman SG. Pharmacotherapy guided by genomic analysis, molecular modeling, and functional profiling can attenuate neuropathic pain in patients carrying the S241T mutation. JAMA Neurol. 2016 Jun 1;73(6):659-87.

SKA2 methylation is associated with decreased prefrontal cortical thickness and greater PTSD severity among trauma-exposed veterans. Sadeh N, Spielberg JM, Logue MW, Wolf EJ, Smith AK, Lusk J, Hayes JP, Sperbeck E, Milberg WP, McGlinchey RE, Salat DH, Carter WC, Stone A, Schichman SA, Humphries DE, Miller MW. DNA methylation of the SKA2 gene in blood indexes points to its potential value as a biomarker of stress exposure and susceptibility. Mol Psychiatry. 2016 Mar;21(3):357-63.

Emotion regulatory brain function and SSRI treatment in PTSD: neural correlates and predictors of change. MacNamara A, Rabinak CA, Kennedy AE, Fitzgerald DA, Liberzon I, Stein MB, Phan KL. Patients who show the most improvement from SSRIs are those who showed the least activation of the right ventrolateral prefrontal cortex before treatment. Neuropsychopharmacology. 2016 Jan;41(2):611-8.

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Genomics Fact Sheet

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VA and other U.S. Government Online Resources

Genomic medicine program advisory committee, Department of Veterans Affairs

MAVERIC (Massachusetts Veterans Epidemiology Research and Information Center), Department of Veterans Affairs

Providence VA Medical Center Genomics Laboratory, Department of Veterans Affairs

Million Veteran Program reaches milestone in Arizona, VA VAntage Point Blog, Aug. 25, 2017

Tri-agency partnership working to tailor cancer care based on genes, proteins, VA News Release, Aug. 23, 2016

VA leads the way on genetic research, VAntage Point Blog, Aug. 9, 2016

Million Veteran Program draws on the power of collaboration, VA VAntage Point Blog, July 22, 2016

VA enlists IBM's Watson Health technology in the war on cancer, VA VAntage Point Blog, June 29, 2016

The VA precision oncology program and a learning healthcare system—wearing the short white coat, VA VAntage Point Blog, Aug. 25, 2015

Genome, NCBI

National Human Genome Research Institute, National Institutes of Health

Cancer Genomics Research, National Cancer Institute, National Institutes of Health

Public Health Genomics, Centers for Disease Control and Prevention

Genomic Science Program, U.S. Department of Energy

Drugs: Genomics, U.S. Food and Drug Administration

Genomics, HealthyPeople.gov

Roundtable on Genomics and Precision Health; National Academies of Science, Engineering and Medicine


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