Highlights of VA research on genetics
April 17, 2019
This month, our focus is on research into the genetic basis of diseases and the development of precision medicine—the practice of using a person's genes, proteins, and other individual traits to identify the best treatments.
VA uses genomic medical research to find new health care solutions and move those into Veterans' care. It has a large and diverse patient population, an integrated network of basic research and clinical programs, and an electronic medical record that offers a rich source of clinical data. New knowledge about the role of genes in health and disease holds the promise of developing safer, more effective, personalized treatments for many conditions. VA physicians are starting to 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 Research in Action
Precision Oncology Program
VA patients nationwide with a common form of lung cancer now routinely have their tumors genetically sequenced to help determine the best therapy, thanks to a program initiated by researchers and clinicians in VA's New England region. The program is one of several efforts launched by VA in the area of precision oncology.
VA Research Currents
Hormone analogs as medical treatment
VA researchers aim to learn whether a genetic test can help patients and doctors choose the right statin medication, with an eye toward minimizing the muscle pain that sometimes occurs with the drugs.... (08/28/2018)
Podcast: VA researcher hopes genetic test can help in choosing right drug to reduce high cholesterol
Gene transfer improves diabetes-linked heart ailment
Researchers with VA and the University of California San Diego have shown that a gene transfer technique can combat heart dysfunction caused by diabetes.... (03/27/2019)
Large genome study leads to better understanding of high blood pressure
A large, international genetic study using Million Veteran Program data has identified more than 200 gene variants that could contribute to high blood pressure. The study also identified over 200 drugs currently used to treat other diseases that could potentially be repurposed to treat high blood pressure.... (02/06/2019)
Researchers explore Vet preferences for receiving results from genetic tests
A VA study is exploring Veterans' preferences for receiving the results of genetic tests they complete as part of research, such as the Million Veteran Program.... (12/20/2018)
MVP study on cholesterol genetics could lead to new treatments for heart disease, diabetes
Using data from VA's Million Veteran Program, a team led by VA and Stanford researchers has identified three genetic mutations that govern cholesterol levels.... (10/24/2018)
Gene variant may increase psychiatric risk after TBI
A gene variant known to predict Alzheimer's risk was linked to worse psychiatric symptoms in those with a traumatic brain injury. Study participants with the gene variant and at least one TBI had more severe PTSD, anxiety, and depression, compared with TBI patients without the same variant.... (04/25/2018)
Who's in MVP?
Selected statistics from a recent review of the demographic, military, and health characteristics of Veterans enrolled in VA's landmark Million Veteran Program.
VA Research News Briefs
Gene variant interacts with stress to accelerate aging
Psychological stress was linked with advanced cellular aging in people with a specific gene variant, in a VA Boston Healthcare System study. Researchers looked at the genotypes of 309 Veterans to see how variants of the longevity gene klotho affected biomarkers of epigenetic age. Epigenetic age refers to how much DNA methylation (a process in which methyl molecules attach to DNA molecules, which can hamper DNA transcription) has occurred, and can be used as a biomarker of how much cells have aged. In some people, epigenetic age can exceed chronological age, which can predict higher mortality risk. They found that a specific form of the gene (rs9315202) interacted with PTSD, sleep disturbances, and pain to predict accelerated epigenetic age. This gene variant also interacted with PTSD to predict inflammation and lower white-matter neural integrity. A different form of the same gene (rs9527025) predicted a slowed epigenetic age. The results suggest that enhancement of the protein produced by the klotho gene could be a treatment target for patients with this gene variant, say the researchers. (
, March 11, 2019)
Brain, Behavior, and Immunity
Cheese may increase prostate cancer risk for men with gene variant
The amount of cheese eaten may interact with specific gene variants to greatly increase the risk of prostate cancer, found a VA Portland Health Care System study. Researchers studied the genomes of 187 patients with prostate cancer and 306 controls without cancer. They looked at how 31 different dietary factors interacted with six genes known to be related to prostate cancer risk. They found that, for patients with a specific variant of one of the genes, each additional daily serving of cheese increased the risk of prostate cancer 16-fold.
Past research has linked dairy to prostate cancer risk. In the new study, prostate cancer risk decreased by 37 percent per daily serving of fruits in the same group. The results suggest that patients’ diet and genetic variation can interact to affect their risk of prostate cancer, say the researchers. (12 th Annual Multi-Institutional Prostate Cancer Program Retreat, March 3, 2019)
Large genome study leads to better understanding of high blood pressure
Photo by Jeff Bowen
A large international genetic study that included several VA researchers has identified more than 500 new gene locations that affect blood pressure. The project is the largest genetic study of blood pressure to date, involving more than 1 million participants. It included data from VA’s Million Veteran Program. By comparing participants’ genetic data, researchers identified 535 new locations on the human genome that influence blood pressure. The researchers calculate that the new findings increase the knowledge of inheritable blood pressure traits by 27 percent. They call the findings “an important step forward” in understanding how genes affect blood pressure. (
, October 2018) Nature Genetics
Study explains gene mutation’s link to ALS
Researchers at the VA Lexington Medical Center and University of Kentucky have shown how a gene mutation may contribute to the development of amyotrophic lateral sclerosis (ALS). Mutation to a gene called fused in sarcoma (FUS) are known to contribute to some cases of inherited ALS. The researchers showed that this mutation can suppress protein translation and interfere with how RNA functions in the body. The mutated proteins generated by the FUS gene disrupt an RNA quality-control pathway, which damages neuronal maintenance and function. Because this mutation suppresses how proteins are translated within cells and disrupts how RNA regulates cell activity, it likely contributes to the motor cell death seen in ALS. According to the researchers, the results will add to the understanding of both how this specific mutation can lead to inherited ALS, and more generally how ALS develops.
( , Nov. 19, 2018)
Proceedings of the National Academy of Sciences
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