ABOVE: The Lieber Institute’s Rahul Bharadwaj examines brain tissue.
LIEBER INSTITUTE FOR BRAIN DEVELOPMENT
Search among the millions of volunteers in the world’s brain-based genomic studies, and you will be hard-pressed to find people of African ancestry. The largest meta-analysis of genome-wide association studies (GWAS) of Parkinson’s disease to date, for example, didn’t include any individuals of primarily African descent among its more than 1.4 million participants, nor did a 2019 meta-analysis of GWASs examining depression. Only 4 percent of all neurological disorder research contained in the GWAS database of the National Human Genome Research Institute includes minority participants.
Databases such as these are critical to research on brain disorders and to genetics-based precision medicine. Yet the lack of data from non-Europeans means that researchers know very little about the genetic variants associated with disease risk in people of African descent, or about genetic biomarkers for disease severity, drug response, or side effects.
This lack of representation so stunned Daniel Weinberger, the director of the Johns Hopkins University–affiliated Lieber Institute for Brain Development, that he published a paper in Neuron this summer addressing the lack of African representation in neuroscience. It was troubling, he says, to acknowledge his own institution’s culpability. “We felt that we, like many people in biomedical research, had underexplored this ancestry, and we became conscious of the fact that most of what we were publishing
. . . were studies on people of European ancestry,” Weinberger tells The Scientist. “This was no longer an acceptable thing for our institute to be doing.”
We became conscious of the fact that most of what we were publishing . . . were studies on people of European ancestry.
—Daniel Weinberger, Lieber Institute for Brain Development
By then, Weinberger had also helped establish an initiative rooted in the community surrounding the Lieber Institute’s laboratory in Baltimore. He and his collaborators set up the African Ancestry Neuroscience Research Initiative (AANRI) in 2019 as a partnership between the institute, the African-American Clergy Medical Research Initiative (AACMRI), and Morgan State University, a historically Black college or university (HBCU), with the intention of increasing diversity among research participants and creating a more diverse community of neuroscientists. The Lieber Institute has been collecting brain donations since 2010, including roughly 700 brains donated by the relatives of people of African descent. According to Weinberger, it’s the largest and most well-curated collection of African ancestry brain tissue in the world.
The initiative, now led by Hathaway and researchers at the Lieber Institute and Morgan State, is working to systematically analyze these samples in three phases. During the first phase, which began in early 2020, researchers are extensively sequencing 200 brains, including DNA, RNA, bisulfite (methylation detection), and peptide sequencing. COVID-19 put the work on pause earlier this year, but the team plans to usher another 300 brains through phase one before moving into phase two, when a subset of those 500 brains will undergo single-cell sequencing and multi-omics to study gene expression. Phase three will look back over the previous two phases and add samples to fill any remaining information gaps. The data will be shared publicly throughout the process, according to Weinberger.
While several other organizations, including the Broad Institute of MIT and Harvard University and the National Institutes of Health, have launched their own efforts to improve diversity in genomics research, what sets the AANRI apart is its community buy-in, says community leader Reverend Alvin Hathaway. Having met with descendants of the infamous Tuskegee Experiment—during which Black men were deceived about treatment for syphilis by researchers studying the disease—Hathaway says, “I know suspicion. I understand distrust.” He facilitated the partnership with Morgan State, which will include the AANRI in its curriculum, host an annual symposium, and send faculty and students to the Lieber Institute for collaborations. Hathaway has also leveraged connections with state officials, financiers, doctors, and educators to bring in funding totaling more than $3 million.
Partnerships with HBCUs will put data directly in the hands of scientists of color, says Mima Akinsanya, a neuroimmunology fellow at the NIH who is not involved in the AANRI. “You can’t say that you are interested in diversity or recruitment of African-Americans and not have any connection with an HBCU.” Akinsanya adds that having a member of the clergy involved in the initiative will help reassure the public about research integrity.
One of the most immediate priorities of the AANRI is to better understand how genetic and racial diversity manifests in disease. People of African ancestry fall into some of the world’s most genetically diverse lineages, and genome-wide “polygenic risk scores” used to predict illness based on data from people of European ancestry are significantly less useful in assessing risk within African descendants. Including more individuals in ongoing research—and therefore capturing more of the diversity inherent in the human genome—will make these scores more predictive for a broader sweep of people, Weinberger says.
With a more complete understanding of the scope of human diversity, researchers could also design better animal models to study mental health disorders in humans, says Bianca Jones Marlin, a neuroscientist at Columbia University who studies the epigenetic impacts of trauma and was not involved in the AANRI. Human GWAS help Marlin know which genes to target when designing her animal experiments, she explains. “As researchers, we should dive at the opportunity to diversify our pool because it’s going to lead to better data,” she says. “We’re hungry for that as scientists.”
Understanding more about how genetic diversity influences an individual person’s susceptibility to disease could lead to advances in precision medicine that benefit all, agrees Kafui Dzirasa, a neuroengineer at Duke University Medical Center and one of Weinberger’s coauthors on the Neuron paper. “Locked within these genetic differences, there might be medications that could be created” to better take each individual’s genetic background into account, he says. “There’s an important case to be made around equity, but there’s also an important scientific case around biological discovery that advances health for everyone.”
Clarification (December 2): The fifth paragraph of this article has been updated to list current members of the initiative, which no longer includes the AACMRI.
