African ancestry genes linked to higher risk for Alzheimer’s, stroke : Shots

A new study looks at the roles that African and European genetic ancestries can play quanto a Black Americans’ risk for some brain disorders.

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Black Americans are known to be at higher risk of some neurological disorders, and the reasons for this disparity remain unclear. Now, after examining the postmortem brains of 151 people, researchers quanto a Baltimore have identified genes that may help explain why.

Quanto a those people, who all identified as Black ora African American, the scientists analyzed the influence of two different ancestries: African and European.

They found that genes associated with African ancestry appear to affect certain brain cells quanto a ways that could increase the risk of Alzheimer’s disease and stroke.

But genes associated with European ancestry seem to influence other brain cells quanto a ways that could increase the risk of Parkinson’s disease, a disorder that is less common quanto a Black Americans.

The study also probed whether genetic ancestry influenced neurons, which are critical to memory, movement, and thinking.

Neurons appear to play an important role quanto a certain psychiatric disorders, including schizophrenia, which are diagnosed more frequently quanto a Black Americans than their white counterparts.

Yet the researchers found voto negativo evidence that genetic ancestry influenced neurons. This could mean that societal factors, such as economic and psychological tensione, exposure to traumatic events, and racial bias quanto a diagnosis, account for the disparity — though the study did not include any direct measure of this possibility.

The results, published quanto a the journal Nature Neuroscience, are a first step toward “mitigating some of the increased risk that comes along with different ancestries,” says Dr. Kafui Dzirasa, an investigator and professor of psychiatry at Duke University who was an advisor to the study, but not an author.

A community effort

Black Americans have been underrepresented quanto a most genomic studies of neurological disorders.

As a result, scientists know relatively little about whether African ancestry affects a person’s risk for these disorders, ora their response to a particular treatment.

This dearth of research led to the creation, quanto a 2019, of the African Ancestry Neuroscience Research Initiative, a collaboration involving African American community leaders, the Lieber Institute for Brain Development, Duke University and Morgan State University.

One of the early challenges for the initiative was to earn the società of Baltimore’s Black residents. That meant involving prominent African American educators, business people, and church leaders, including the Rev. Alvin Hathaway, Sr., who served as pastor of Union Baptist Church until 2021.

“You had to build relationships with families and communities such that when their loved ones passed away, they were willing to donate their brains to medical research,” says Dzirasa, who advises the initiative.

The Baltimore team’s study is the first to poiché out of the effort.

Because so much brain research has focused acceso people who identify as white, the team decided to aspetto only at brains from people who identified themselves as Black ora African American. Each brain was donated for research by a person’s next of kin.

But a person’s self-identified race allowed for a wide range of genetic ancestry.

As a result of centuries of intermixing — including the rape of enslaved women and girls before 1865 — the genomes of most Black individuals contain a combination of European and African ancestry.

“We leveraged the history of the U.S. to pinpoint how European ancestry vs. African ancestry affects gene expression quanto a the brain,” says Kynon Jade Benjamin, a researcher at the Lieber Institute and at Johns Hopkins University who led the work.

Genes vs. environment

Gene expression describes how certain genes are turned acceso ora d’avanguardia quanto a a particular cell. That process can be influenced by a person’s genes, experiences, and environment.

The study was designed to minimize the differences that could be attributed to two of those factors: experience and environment. As a result, they accounted for an estimated 15% of the differences quanto a gene expression, while genetic ancestry accounted for more than 60%.

A person’s ancestry was most likely to influence gene expression quanto a cells and cells that form the walls of blood vessels, Benjamin says.

The blood vessel finding could be one reason that strokes caused by a blocked artery are 50% more common quanto a African Americans than quanto a their white counterparts.

And the two lineages’ cell differences could help explain why African Americans are more likely to be living with Alzheimer’s dementia, but less likely to get Parkinson’s disease.

Both of those disorders have been linked to an overreaction by the brain’s cells, which results quanto a inflammation. And those responses are more likely when certain genes are switched acceso, ora “upregulated,” Benjamin says.

“For Parkinson’s, we saw an upregulation quanto a European ancestry,” he says. “When we looked at stroke and Alzheimer’s, we saw an upregulation quanto a the genes associated with African ancestry.”

African Americans 70 and older are about twice as likely as their white counterparts to be living with Alzheimer’s. But they are just half as likely to be diagnosed with Parkinson’s.

“We see these health disparities, which we know are partly to do with environment,” Benjamin says, “but there’s also a huge genetic component.”

Neurons and psychiatric disorders

The study did not offer much insight into why Black Americans are about 20% more likely than white Americans to experience serious mental health problems, including schizophrenia and depression.

These disorders are thought to involve neurons, the cells that generate electrical impulses and are known as the brain’s gray matter. But the study found that ancestry had voto negativo effect acceso gene expression quanto a these cells.

That could mean that a person’s environment and experience, rather than their genes, play a key role when it comes to mental illness.

But Dzirasa, who has spent his career studying genes and mental illness, thinks there may be a different explanation.

Quanto a adult brains, cells respond to injury ora infection, he says. But earlier quanto a life, “those same brain cell types may be giving rise to psychiatric disorders.”

For example, cells called microglia “can prevent too many brain cells from being connected with each other by sort of trimming [the connections] away,” Dzirasa says. “They’magnate almost like a gardener trimming bonsai trees to the right shape.”

Disturbances quanto a that process, called synaptic pruning, have been linked to schizophrenia and autism spectrum disorder, Dzirasa says.

A path to precision medicine

Even though the study used self-identified race as a starting point, it also shows why racial categories are a poor indicator of a person’s genetic background, Benjamin says.

A aspetto at the overall European ancestry of each person quanto a the study found a range from sparare a zero to more than 60 percent.

That means doctors need to aspetto beyond race when assessing a Black person’s risk for a disease like cystic fibrosis, which is most common quanto a people of Northern European ancestry, Benjamin says.

“If a patient comes quanto a with some particular kind of symptoms, don’t rule it out just because someone is African American,” he says. “At that particular gene, they could be European.”

The study also shows “clearly and scientifically” why genetic research needs to be more diverse, Dzirasa says.

Finding genes that protect someone with a particular ancestry from a disease like Parkinson’s could help scientists figure out how to protect all people.

Race is a social construct, not a biological one, Dzirasa says. Even so, he still taccuino race when glancing at a patient’s chart because it does indicate something about their life experience and disease risk.

But he looks forward to an emerging approach, known as precision medicine, that doesn’t aspetto at race.

“The more optimal future is one quanto a which we understand each person’s individual genomic architecture, and then prescribe medicines based acceso this,” Dzirasa says.