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By Jennifer Couzin-Frankel
Earlier this week, the Lieber Institute for Brain Development, a non-profit organization housed at the Johns Hopkins University School of Medicine in Baltimore, Maryland, announced a new neuroscience research initiative aimed at to fill a gaping void in medicine: the interaction between brain diseases and their genomics. drivers among African Americans. The goal is to better understand the impact of brain diseases on this population, which has been profoundly underrepresented in neuroscience research. To create trust between African Americans in Baltimore and beyond, the company includes a partnership with the African American Medical Clergy Initiative, a group of clergy leaders in the city. Lieber's African-American scientists are already involved, but project leaders hope to tap into those of other institutions as work progresses.
The effort builds on Lieber's growing brain library, which currently has about 3,000 brains, with more than 400 new brains collected each year, all donated by the next of kin. Many come from young and middle-aged people who suddenly die of suicide, overdose of drugs, or other causes. Although most brains are of European origin, more than 700 are of African-American origin. Despite the growing recognition that African Americans are under-represented in medical research – and faced with discrimination and other challenges that may increase health risks – studies of brain diseases in this population have delayed, "said Daniel Weinberger, director of the institute.
ScienceInsider has been talking with Weinberger, a psychiatrist and schizophrenia researcher, who came to the Lieber Institute in 2011 from the National Institute of Mental Health. The conversation was changed for brevity and clarity.
Q: Why is it important to study brain diseases in African Americans in particular?
A: In general, the data suggest that all neuropsychiatric diagnoses are 20% more common in African-American communities than in communities of European descent. Alzheimer's disease is about twice as common. Psychiatric disorders, in particular, have differences in frequency, response to treatment and how to manifest themselves. the [U.S. Centers for Disease Control and Prevention] recently came out with a report that [showed] suicides among African-American children had become more common. It was a huge surprise.
And the other thing that has become clear, like these big GWA [genome-wide badociation] studies began to emerge – they were almost entirely based on individuals of European origin. They are much, much less relevant [for African-Americans]. In the world of schizophrenia, to which I played an important role, we can predict something like almost 20%. [of risk based on genetics among Europeans]. But in the African-American population, it is less than 5%. We know that APOE4 [an important Alzheimer’s risk gene] is much less a risk factor in the African-American population, although Alzheimer's disease is much more common. In many ways, the brain is the most complex problem, but it is the one that is least represented in this effort. [to include African-American samples in medical research].
It's the submerged part of the iceberg that has been left unexplored, basically.
Q: If African-Americans are more likely than whites to suffer from a serious mental illness, what about social factors such as discrimination?
A: We make a long story by taking each donation to the deposit. The team talks to the next of kin. We acquire all records available on the deceased – school records, hospital records. We talk to their doctors. It takes weeks. We have a lot of information about the life of the individual.
There is a lot of information now that toxic stress in young children, whatever its definition, creates an increased risk for many medical conditions, not just psychiatric disorders. The badumption is that it changes the [gene expression] in many cells of the body. There is good reason to believe that people who have been exposed early in life to enormous stress, leave a mark on their genome. We will theoretically be able to examine this question and its impact on the treatment of genes in certain brain cells. And then, it's the Holy Grail, it could give an idea of how to save [others].
Q: Do you think you have all these brains but not the resources to study them?
A: It's safe. In Nature Genetics, there was a historical sequencing document of 900 African-American genomes. The takeaway message was staggering: 10% of the African American DNA sequence is missing from the human genome reference sequence, which is used in all current human studies.
We want to catch up with a lot of things that have already been done in [the brains of people of European-American descent]. We want to do a lot of sequencing of RNA. We are increasingly focusing on trying to identify different cells responsible for these specific genetic risk effects. It's a huge project.
We have African-American brains of prenatal life, early childhood. Prematurity is much more prevalent in the African-American community. We must explore this whole issue of development in the context of genetic variation.
And we have a lot of brains with the diagnosis of schizophrenia, depression, bipolar disorder, addiction. There are a multitude of questions to ask.
Q: What about money? You are asking the state of Maryland for $ 5 million to help bring this project to fruition.
A: State demand is $ 2.5 million a year for two years. This would re-launch the generation of extensive data and would also generate much more interest for this project.
Q: Are there unique challenges in conducting genomic brain studies versus genomic heart studies, for example?
A: The phenotype [what’s visible] has different levels of badysis. One is the age of the person. Another could be the diagnosis. The third level is the expression, splicing, modification of the regulation of a gene – the expression of a gene in the brain, which constitutes the model of how where you build the brain and how the brain reacts to the environment. There are so many parts in the brain, [so] a lot of cells in it. We collect living cells from people with our brains and collaborate with stem cell groups across the country. There are parts of [brain]like the dura [the membrane surrounding the organ]who survive for days after death. We live [cell] lines of these brains.
There has been tremendous abuse of the African-American community by the biomedical community. As a result, there is a lot of mistrust in the African-American community. Every brain we get is given by the next of kin. Obtaining consent and donation must be done within 24 hours of death. We have essentially the same donation frequency – 70% – of African-American families [who are approached] that we have from American-European families. That says a lot about one of the issues that has been troubling this research for some time.
Q: It seems that the partnership with the leaders of the Baltimore clergy is a way to solve this problem. How it works?
A: [The goal is] build trust. It is to improve the possibilities of precision medicine. This train, which left the station, may be leaving [African-Americans] behind. We brought together a group of community leaders from the African-American community [in Baltimore]directed by Alvin Hathaway [principal of the African-American Clergy Medical Research Initiative], an extraordinary man. We met 23 leaders. Our hope is to set up an advisory group, which would include community leaders as well as scientists from across the country.
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