A new study examines how African American and European genetic ancestry influences the risk of brain disease in black Americans. TEK IMAGE/SCIENCE PHOTO LIBRARY/Getty Images Hide caption
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Black Americans are known to be at higher risk for several neurological disorders, but the reasons for this disparity remain unclear. Now, researchers in Baltimore have examined the postmortem brains of 151 people and identified a gene that may help explain why.
The scientists analyzed the influence of two different ancestries, African and European, in these people who identify as black or African American.
Researchers have found that genes associated with African ancestry may affect certain brain cells in ways that could increase the risk of Alzheimer's disease and stroke.
But genes associated with European ancestry appear to affect other brain cells in ways that could increase the risk of Parkinson's disease, which is less common in black Americans.
The study also investigated whether genetic ancestry influences neurons important for memory, movement and thought.
The neurons appear to play an important role in certain psychiatric disorders, including schizophrenia, which is diagnosed more often in black Americans than whites.
However, the researchers found no evidence that genetic ancestry influenced the neurons, which could mean that social factors such as economic and psychological stress, exposure to traumatic events, or racial bias in diagnoses are responsible for the disparity, although the study did not include direct measures of this possibility.
The findings, published in the journal Nature Neuroscience, are a first step toward “mitigating some of the increased risk associated with ancestry differences,” said Duke University researcher and professor of psychiatry Dr. Kahui Djirasa, who advised on the study but was not an author.
Community Effort
Black Americans are underrepresented in most genomic studies of neurological diseases.
As a result, scientists know little about whether African ancestry affects risk of these diseases or response to certain treatments.
This lack of research led to the creation of the African Ancestry Neuroscience Research Initiative in 2019, a collaboration between African American community leaders, the Lieber Institute for Brain Development, Duke University and Morgan State University.
One of the effort's early challenges was winning the trust of Baltimore's black residents, which meant bringing in prominent African-American educators, businessmen and church leaders, including the Rev. Alvin Hathaway, who served as pastor of Union Baptist Church until 2021.
“We had to build relationships with families and communities so that when their loved ones died, they would be willing to donate their brains for medical research,” says Jirasa, who serves as an adviser to the effort.
The Baltimore team's study is the first to come out of this effort.
Because most brain studies to date have focused on people who identify as white, the team decided to look only at the brains of people who identify as black or African-American, each of whose brains was donated for the study by a close relative.
However, the race that a person identifies with allows for a wide range of genetic ancestry.
As a result of centuries of admixture, including the rape of enslaved women and girls before 1865, the genomes of most black people contain a combination of European and African ancestry.
“We've used the history of the United States to pinpoint how European and African ancestry influences gene expression in the brain,” said Quinones Jade Benjamin, a researcher at the Lieber Institute and Johns Hopkins University who led the study.
Genes vs. Environment
Gene expression describes how specific genes are turned on or off in specific cells, a process that can be influenced by an individual's genes, experiences, and environment.
The study was designed to minimize variance attributable to these two factors: experience and environment, which accounted for an estimated 15% of the variance in gene expression, and genetic ancestry for more than 60%.
Benjamin says a person's ancestry is most likely to influence gene expression in immune cells and cells that make up blood vessel walls.
The vascular findings may be one reason why strokes caused by blocked arteries occur 50% more often in African-Americans than whites.
And differences between these two lines of immune cells may help explain why African Americans are more likely to suffer from Alzheimer's disease but less likely to develop Parkinson's disease.
Both diseases have been linked to an overactivity of immune cells in the brain, which leads to inflammation, and this immune response is more likely to occur when certain genes are activated, or “upregulated,” Benjamin said.
“For Parkinson's disease, we saw increased gene expression in those of European ancestry,” he says, “and for stroke and Alzheimer's disease, we saw increased gene expression in genes associated with African ancestry.”
African Americans over age 70 are nearly twice as likely as whites to suffer from Alzheimer's disease, but only half as likely to be diagnosed with Parkinson's disease.
“We know that these health disparities are partly related to the environment,” Benjamin says, “but there's also a big genetic component.”
Neurons and mental illness
The study didn't shed much light on why black Americans are about 20% more likely than white Americans to experience serious mental health problems, such as schizophrenia and depression.
These disorders are thought to involve neurons, the cells that generate electrical signals in the brain's grey matter, but the study found that ancestry does not affect gene expression in these cells.
This could mean that a person's environment and experiences, rather than genes, play a key role when it comes to mental illness.
But Djirasa, who has spent his career studying genes and mental illness, thinks there may be another explanation.
In the adult brain, immune cells respond to injury and infection, he says, but at younger stages of life, “the same types of brain cells may be driving psychiatric disorders.”
For example, immune cells called microglia “can prevent brain cells from becoming too connected to each other.” [the connections] “It's like a gardener pruning a bonsai tree into the right shape,” says Jirasa.
Djirasa said disruptions to this process, called synaptic pruning, have been linked to schizophrenia and autism spectrum disorders.
The road to precision medicine
While the study used self-identified race as a starting point, Benjamin said it also shows why racial categories are a poor indicator of an individual's genetic background.
The overall European ancestry of each individual in the study was found to range from zero to more than 60 percent.
That means doctors need to look beyond race when assessing black people's risk for diseases like cystic fibrosis, which is most common in people of Northern European descent, Benjamin said.
“If a patient comes in with a certain symptom, don't rule them out just because they're African-American,” he says. “With that particular gene, they could be European.”
The study shows “clearly and scientifically” why genetic research needs to become more diverse, Jirasa said.
Finding genes that protect people of certain ancestry from diseases like Parkinson's could help scientists find ways to protect everyone.
Race is a social, not biological, construct, Dr. Jirasa says, but he still looks at it when he reviews patients' medical records because it can say something about their life experiences and risk for disease.
But he is hopeful about a new approach called “precision medicine” that doesn't take race into account.
“A more optimal future would be one in which we understand each person's individual genomic makeup and prescribe medicines based on that,” Jirasa says.
