Genetic ancestry contributes to the brain gene expression in black Americans


Scientists seeking to counter the neglect of African Americans in neuroscience research have found evidence that genetic ancestry is responsible for the increased prevalence of certain neurological disorders, such as Alzheimer’s disease and stroke, and decreased prevalence of others, including Parkinson’s disease, in Black Americans, according to new research published in the journal Nature Neuroscience

In contrast, the scientists did not find evidence that genetic ancestry is responsible for differences in the prevalence of psychiatric disorders and behavioral traits, such as schizophrenia and depression, across populations of European or African ancestry. Instead, those differences may be driven by variation in environmental exposures. 

The study, the first to broadly explore specifically how African ancestry influences gene function in the human brain, is the first research to emerge from the African Ancestry Neuroscience Research Initiative. The initiative, known as AANRI, is a collaboration between the Lieber Institute — located on the Johns Hopkins medical campus in Baltimore — as well as African American community leaders from the city and Morgan State University, a public historically Black university also located in Baltimore. 

“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,” says the senior author on the study.  

The research notes that people of African ancestry account for less than 5% of data used in large-scale brain disorder research but are 20% more likely to experience a major mental health crisis, and up to twice as likely to manifest Alzheimer’s disease.  

Lieber Institute scientists measured the genes present in over 425 brain samples from African American individuals, all medically healthy people. In addition, they focused on how the environment might impact the regulation of genes in the brain, a field of study called epigenetics. The scientists found that about 15% of the variation in gene expression in the brain was based on environmental differences in people of African ancestry.   

“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,” says the author. “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.”  

Lieber Institute researchers identified more than 2,500 genes in the brains of individuals of African ancestry with significant differences in expression related to the proportion of each individual’s degree of African versus European ancestry. People of African descent are, in general, of mixed ancestry, with a range of about 0-60% European ancestry. The scientists were able to explore how much this ancestral variation within each brain predicted corresponding variation in gene abundance. The results showed that ancestry-informed genes were especially important in nonneuronal cells, particularly immune and vascular tissue cells.  

This research confirms previous mechanisms that have been observed in the importance of vasculature in stroke. In fact, over 25% of the genetically determined probability of a stroke could be predicted by genes in vascular cells based on African ancestry proportion.  

Even more strikingly, the scientists confirmed the importance of immune cells in liability for Alzheimer’s disease, with 30% of the genetic probability of this illness predictable by genes in immune cells based on African ancestry proportion in each brain.  

The scientists also found differences that posed an advantage to people of African ancestry — for example, the brains from people of African ancestry showed a decrease in the expression of genes related to risk of Parkinson’s disease. This confirms public health data that shows lower rates of Parkinson’s disease in people of African ancestry. 

The findings mean that scientists exploring new therapies to treat neurologic illness should consider targeting both neuronal and nonneuronal cells, such as immune and vascular tissue cells.  

People of African ancestry are chronically neglected in studies that are driving the search for new treatments and cures by revealing genetic factors that influence disease. The Lieber Institute for Brain Development uses genomics and other advanced scientific techniques to learn more about the roots of brain disorders such as schizophrenia, depression, bipolar disorder, PTSD and autism.  

More than 81% of large-scale genomic datasets used in this type of research come from people of European descent, though those of European background make up less than 16% of the world population. Human beings are more than 99% genetically identical. That less than 1% accounts for all human diversity on earth — and that’s the focus of AANRI, says Dr. Weinberger. 

The Lieber Institute is home to the largest collection of postmortem brains for the study of neurodevelopmental disorders in the world. Each of the Institute’s more than 4,300 brains was donated by a recently bereaved family member through a rigorous informed consent process. Lieber Institute scientists used about 425 brain samples from the collection, each from a person of African ancestry who was medically healthy, for the Nature Neuroscience study. 

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, says another author.  

“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,” says the senior author.

https://www.nature.com/articles/s41593-024-01636-0

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fanalysis-of-gene&filter=22

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