Genetic risk factor for CTE detected

November 03, 2018

(Boston)--Researchers have identified a genetic variation that may influence chronic traumatic encephalopathy (CTE) disease severity.

TMEM106B is one of the first genes to be implicated in CTE. It may partially explain why some athletes present with severe CTE symptoms while others are less affected despite similar levels of head trauma.

The study provides preliminary evidence that this genetic variation might help predict which individuals are at greater risk to develop severe CTE pathology and dementia, according to the researchers. It also provides insight into the disease mechanism underlying CTE, which could aid in the development of biomarkers for diagnosis during life and in the identification of targets for treatments.

Researchers from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System (VABHS) studied 86 former contact-sport athletes whose brains were donated to the VA-BU-CLF brain bank and found to have evidence of CTE, but no other pathology. The athlete brains were examined for genetic variation in TMEM106B, a gene thought to be involved in the brain's inflammation system. Overall, the genetic variation was not different in those with CTE compared to those without. "However, among the athletes with CTE, variation did predict increased CTE pathology and brain inflammation. Additionally, the risk allele increased the likelihood of developing dementia by 2.5 times suggesting the variant might predict an increased risk for developing the symptoms of CTE," explained first author Jonathan Cherry, PhD, postdoctoral fellow in neurology at BUSM.

"These findings may help explain why some individuals experience more severe CTE related outcomes while others are spared despite similar exposure to contact sports. By better understanding why some individuals are more at risk for CTE, we can identify novel therapeutic targets to help treat all with the disease," said corresponding author Thor Stein, MD, PhD, neuropathologist at VA Boston Healthcare System and assistant professor of pathology and laboratory medicine at BUSM.

The researchers caution that it is still unclear what variation in TMEM106B means on an individual level for people at risk for CTE. Therefore, genetic testing for clinical care is not currently recommended.

The study appears in the journal Acta Neuropathologica Communications.
-end-
Jesse Mez, MD, MS, assistant professor of neurology at BUSM is the study's co-first author. Ann McKee, MD, Chief of Neuropathology, VA Boston Healthcare Syste, and Director of the BU CTE Center is the co-senior author.

This study received support from National Institute of Neurological Disorders and Stroke (U01NS086659, R01NS078337, R56NS078337, U01NS093334, and K23NS102399), National Institute on Aging (K23AG046377, P30AG13846 and supplement 0572063345, RF1AG057902, RF1AG054156, R56AG057768), US Department of Defense (grant W81XWH-13-2-0064), US Department of Veterans Affairs (I01CX001038), Veterans Affairs Biorepository (BX002466), Veterans Affairs Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (B6796-C), Department of Defense Peer Reviewed Alzheimer's Research Program (13267017), Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095, Department of Veterans Affairs CENC Award I01CX001135, National Center for PTSD, National Operating Committee on Standards for Athletic Equipment, Alzheimer's Association (NIRG-15-362697, NIRG-305779, AARF-17-529888), Nick and Lynn Buoniconti Foundation, Concussion Legacy Foundation, Andlinger Family Foundation, WWE, and NFL.

EMBARGOED by Acta Neuropathologica Communications until Nov. 3, 2018, 9 pm, ET Contact: Gina DiGravio, 617-358-7838, ginad@bu.edu

Boston University School of Medicine

Related Genetic Variation Articles from Brightsurf:

How genetic variation gives rise to differences in mathematical ability
DNA variation in a gene called ROBO1 is associated with early anatomical differences in a brain region that plays a key role in quantity representation, potentially explaining how genetic variability might shape mathematical performance in children, according to a study published October 22nd in the open-access journal PLOS Biology by Michael Skeide of the Max Planck Institute for Human Cognitive and Brain Sciences, and colleagues.

Genetic variation unlikely to influence COVID-19 morbidity and mortality
A comprehensive search of genetic variation databases has revealed no significant differences across populations and ethnic groups in seven genes associated with viral entry of SARS-CoV-2.

Researchers find pronghorn exhibit little genetic variation despite landscape obstacles
While previous research shows landscape features such as major highways restrict the daily and seasonal movements of pronghorn and increase mortality risk, this study found little, if any, evidence that these barriers affect genetic connectivity among Wyoming pronghorn.

gnomAD Consortium releases its first major studies of human genetic variation
For the last eight years, the Genome Aggregation Database (gnomAD) Consortium (and its predecessor, the Exome Aggregation Consortium, or ExAC), has been working with geneticists around the world to compile and study more than 125,000 exomes and 15,000 whole genomes from populations around the world.

Individual genetic variation in immune system may affect severity of COVID-19
Genetic variability in the human immune system may affect susceptibility to, and severity of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease (COVID-19).

Genetic variation not an obstacle to gene drive strategy to control mosquitoes
New research from entomologists at UC Davis clears a potential obstacle to using CRISPR-Cas9 'gene drive' technology to control mosquito-borne diseases such as malaria, dengue fever, yellow fever and Zika.

Genetic variation gives mussels a chance to adapt to climate change
Existing genetic variation in natural populations of Mediterranean mussels allows them to adapt to declining pH levels in seawater caused by carbon emissions.

A genetic tug-of-war between the sexes begets variation
In species with sexual reproduction, no two individuals are alike and scientists have long struggled to understand why there is so much genetic variation.

Scientists identify genetic variation linked to severity of ALS
A discovery made several years ago in a lab researching asthma at Wake Forest School of Medicine may now have implications for the treatment of amyotrophic lateral sclerosis (ALS), a disease with no known cure and only two FDA-approved drugs to treat its progression and severity.

Genetic variation contributes to individual differences in pleasure
Differences in how our brains respond when we're anticipating a financial reward are due, in part, to genetic differences, according to research with identical and fraternal twins published in Psychological Science, a journal of the Association for Psychological Science.

Read More: Genetic Variation News and Genetic Variation Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.