Genetic ancestry’s contribution to Parkinson’s, brain disorders shown

Study underscores need to consider role of immune, blood vessel cells

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A close-up view of a single DNA strand shows its double-helix structure.
A first-of-its kind study has identified key genes in the brain that explain why Black Americans have a lower incidence of Parkinson’s disease, but are at heightened risks for other brain disorders, including stroke and Alzheimer’s.
“This landmark work enriches our understanding of the role of genetic ancestry in the brain, opens new avenues for the development of ancestry-aware therapeutics, and paves the way for more equitable personalized medicine,” Daniel Weinberger, MD, director and CEO of the Lieber Institute and the study’s lead scientist, said in a press release.
It’s the first study from the African Ancestry Neuroscience Research Initiative (AANRI), a  collaborative endeavor involving the Lieber Institute, which is located at the Johns Hopkins Medical Campus in Baltimore, and area African American community leaders, including Morgan State University, a historically Black public university.
“I’m deeply embedded in the African Ancestry Neuroscience Research Initiative because I can see glimmers of hope,” said Alvin C. Hathaway Sr., co-founder of AANRI and a retired pastor of the historic Union Baptist Church. “I see that we really can accelerate research for people of color. We can help scientists understand what it means to be culturally sensitive to a community.”

Parkinson’s disease and other brain disorders arise from a complex interplay of environmental and genetic risk factors. People of African ancestry account for less than 5% of data in large-scale brain disorder research. This is particularly concerning because the risk of developing brain disorders varies markedly across different genetic backgrounds. For instance, people of African descent exhibit a lower risk for Parkinson’s disease, but are up to twice as likely to develop Alzheimer’s disease compared with other ethnic groups.

More than 81% of large-scale genetic-based studies rely on samples from people of European descent, who represent about 16% of the global population. To ensure equitable treatment and tailored healthcare solutions, it’s crucial to diversify the datasets in brain disorder research to better reflect the variety of genetic backgrounds worldwide.

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The role of ancestry in gene function

The lack of diversity “limits the accuracy of genetic risk prediction and hinders the development of effective personalized neurotherapeutics for individuals of non-European genetic ancestry,” wrote the researchers, who analyzed the genome and transcriptome of more than 425 brain samples from healthy African Americans to investigate how African ancestry influences gene function in the human brain. The genome is an organism’s complete genetic blueprint, while the transcriptome provides a snapshot of gene activity.

The researchers also examined epigenetic changes, collectively known as the epigenome, in the samples. Epigenetics involves mechanisms that modulate gene activity without changing the actual DNA sequence, helping researchers better understand how environmental factors influence gene function.

About 15% of the variation in gene expression in the brain was based on environmental differences in people of African ancestry. Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.

 “We inherit from our parents our DNA, the sequence of our genes, and they inherit their DNA from their parents, who got it from theirs, and so forth and so on,” Weinberger said. “Our genomes are the fingerprints of our near and distant ancestors who have contributed over time and generations various pieces of what becomes our individual genomes.”
African Americans are, in general, of a mixed ancestry, with a range of 0 to 60% European ancestry. More than 2,500 genes in the brains of people of African ancestry showed significant differences in their expression levels that correlated with the proportion of African versus European ancestry in each person.
Further analysis revealed that ancestry-informed genes were particularly important in immune cells and blood vessel cells of the brain. The findings are consistent with studies that show that more than 25% of the risk of a stroke could be predicted by the proportion of African ancestry genes in vascular cells. The presence of African ancestry genes in brain immune cells was also linked with a 30% higher probability for Alzheimer’s disease.
But African ancestry was advantageous in Parkinson’s, with African ancestry genes in the brain correlating with a lower expression of genes linked with the disease. Again, the findings confirm public health data that show lower rates of Parkinson’s disease among people of African descent.
The findings shed light on the intricate biology of disorders like Parkinson’s and Alzheimer’s and how scientists exploring new therapies need to take into account other cells besides neurons, such as immune and blood vessel cells. They also highlight how policies must be tailored to account for social determinants of populations.
“Medications are important interventions for brain disorders, but findings such as these highlight the need for policies that address social determinants of health such as pollution, access to nutritious food, high-quality health care and education,” said Kafui Dzirasa, MD, PhD, an advisor to the AANRI, a professor at Duke University School of Medicine and a Howard Hughes Medical Institute investigator. “As we learn about brain function and think how to better protect against the environment, some of the best things that we should be out there advocating for are policy changes.”

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