New findings from researchers at the U.S. Department of Veterans Affairs (VA) have identified unique genetic markers of dementia in people of African descent from those previously associated with people of European ancestry. The investigative team—which claims this is the largest study of its kind focused on people of African ancestry—used data from the Million Veterans Program (MVP) to help discover new genetic biomarkers that may raise the risk of developing Alzheimer’s disease (AD) and other associated dementias in this under-studied population.
“MVP represents an incredible resource for examining the genetics of many diseases, including dementia,” said study author Mark Logue, a statistician with the VA Boston Healthcare System and National Center for PTSD. “This study is one of the first Alzheimer’s-disease-related studies to come out of MVP. My colleagues and I are working hard to ramp up dementia work in MVP and to team up with other large-scale Alzheimer’s disease and dementia studies.”
To date, the bulk or research of Alzheimer’s disease has focused on white, European populations despite the fact that AD affects a higher proportion of African Americans than those of European ancestry. Like many diseases, AD shares a number of genetic variants that span different ethnic populations, but there are also specific genetic variants that differ based on a person’s ancestry. For instance, genetic variation in the APOE E4 gene is a well-documented indicator of genetic risk for people of European ancestry, while the risk for people with Africa ancestry is about half as strong.
To help address this known disparity, investigators at the Boston VA compared the genomes of 4,000 MVP participants of African ancestry with dementia with more than 18,000 veterans without dementia. A parallel analysis compared the genomes of 7,000 African American participants who had parents with dementia with 56,000 people who reported no such family tie to the disease—a data sample that is more than double previous studies of AD.
The data showed a strong correlation of the risk of developing AD within this population with variants in six genes, including APOE. A significant finding was that four of the genes had not been identified previously as signaling risks in people of African ancestry.
The research team noted that the goal of the study is to close the gap between the knowledge of the risk factors associated with AD among a European population versus the different risk factors of those people with African ancestry. The investigators also noted that these data could also be leveraged to develop more effective, targeted treatments for this population.
According to the research team, the MVP was the best-suited study of this kind as it is one of the most diverse biobanks in the world, incorporating the data of more than 150,000 African American veterans, representing 18% of all participants.
“The sheer size of MVP as one of the world’s largest genetic databases means that it can really push forward what is known about how genes influence dementia risk,” Logue noted.
