VA Boston Health System and PTSD National Center statistician, study author Dr. “MVP is an incredible resource for investigating the genetics of many diseases, including dementia,” said Mark Logue. “This study is one of the first Alzheimer’s disease studies to come out of MVP. My colleagues and I are working hard to strengthen the dementia work at MVP and collaborate with other large-scale Alzheimer’s disease and dementia research.
“The results represent a significant increase in knowledge about the genetic architecture of dementia risk in populations of African ancestry,” Logue said.
People of African descent and other minority groups have historically been underrepresented in genetic research, so this study represents an important milestone, according to the research team.
Dementia and people of African descent
In the United States, African-Americans are more likely to suffer from Alzheimer’s disease than Europeans; however, the largest genetic studies of Alzheimer’s disease study white participants. Although there are genes in Alzheimer’s disease that are consistent across different populations, the researchers explained in the study that specific variants may differ by ancestry. This means that research results using only one ethnic group may not apply to other groups and may hinder the prevention and treatment of dementia. For example, studies have found that a gene variant called APOE E4 carries the greatest genetic risk for Alzheimer’s disease in people of European descent, but the effect of APOE E4 is twice as strong in people of African descent.
Increasing the representation of non-European ancestry populations in genome-wide association studies has been identified as a critical scientific and equity issue in genetic research. The difference in sample sizes between studies of European ancestry and non-European ancestry to date may contribute to health disparities even in minority populations, according to the study.
To address this disparity, Boston VA researchers compared the genomes of more than 4,000 MVP participants of African ancestry with dementia to more than 18,000 Veterans without dementia. The team also conducted a second analysis comparing 7,000 black MVP participants who reported having a parent with dementia versus 56,000 whose parents did not have dementia. This sample is twice the size of the previous largest Alzheimer’s genetic study of individuals of African ancestry.
The results showed associations between dementia risk and variants in six different genes, including APOE. Although many of these genes have been linked to dementia in past genetic studies of people of European ancestry, only two of them have been identified as significant risk factors in people of African ancestry.
Although many of the genetic variants identified in this study were associated with dementia across groups, the specific gene variants associated with dementia risk differed between people of African and European ancestry, meaning that different forms of the same gene may have a causal effect on a person’s dementia risk. by their race.
With more than 900,000 participants to date, MVP is one of the largest genetic research programs in the world. MVP researchers collect genetic information in addition to health, lifestyle, and military exposure data to understand how genes influence health and disease.
MVP is also one of the most diverse genetic programs in the world. More than 150,000 African American Veterans have volunteered to join the MVP, representing 18% of all participants. This means that MVP includes more people of African descent than any other biobank in the world. Through its diversity and the altruism of participating Veterans, MVP strives to close racial gaps in the relationship between genetics and disease.
“As one of the world’s largest genetic databases, MVP’s sheer size means it can advance what is known about how genes influence dementia risk,” Logue said. “Working on the MVP data is an exciting opportunity for a researcher like myself, and I am grateful to all Veterans who agreed to participate in this study.”