New effort aims to study brain diseases in AfricanAmericans By Jennifer Couzin-FrankelMar. 22, 2019 , 2:50 PM New effort aims to study brain diseases in African-Americans Email Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Sign up for our daily newsletter Get more great content like this delivered right to you! Country Click to view the privacy policy. Required fields are indicated by an asterisk (*) Earlier this week, the Lieber Institute for Brain Development, a nonprofit housed at Johns Hopkins University School of Medicine in Baltimore, Maryland, announced a new neuroscience research initiative that aims to tackle a gaping hole in medicine: the interplay between brain diseases and their genomic drivers among African-Americans. The goal is to better understand how brain diseases play out in this population, which has been profoundly underrepresented in neuroscience research. To build trust among African-Americans in Baltimore and eventually beyond, the venture includes a partnership with the African-American Clergy Medical Research Initiative, a group of clergy leaders in the city. African-American scientists at Lieber are already involved, but project leaders hope to engage those at other institutions as the work expands.The effort builds on Lieber’s rapidly growing brain bank, which now stands at about 3000 brains, with more than 400 new brains collected each year, all donated by next of kin. Many are from young and middle-aged people who die suddenly of suicide, drug overdose, or other causes. Although most of the brains are from people of European ancestry, more than 700 are from African-Americans. Despite growing recognition that African-Americans are underrepresented in medical research—and face discrimination and other hardships that can heighten health risks—study of brain diseases in this population have lagged behind, says Daniel Weinberger, the institute’s director.ScienceInsider spoke with Weinberger, a psychiatrist and schizophrenia researcher who came to the Lieber Institute in 2011 from the National Institute of Mental Health. The conversation has been edited for brevity and clarity. Q: Why is it important to study brain diseases in African-Americans in particular?A: In general, data suggest that all neuropsychiatric diagnoses are 20% more frequent in African-American communities than they are in communities of European ancestry. Alzheimer’s disease is about twice as common. Psychiatric disorders, in particular, show differences in frequency, response to treatment, and in how they 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 frequent. That was a huge surprise.And the other thing that became clear, as these large GWA [genome-wide association] studies began to emerge—they were based almost completely on individuals of European ancestry. They’re much, much less relevant [for African-Americans]. In the schizophrenia world, which I’ve been a big part of, we can predict somewhere close to 20% [of risk based on genetics among Europeans]. But in the African-American population, it’s less than 5%. We’ve known that APOE4 [an important Alzheimer’s risk gene] is much less of a risk factor in the African-American population, even though Alzheimer’s is much more common. In many ways, the brain is the most challenging problem but it’s the one that’s least represented in this effort [to include African-American samples in medical research].This is the submerged part of the iceberg that has been left unexplored, basically.Q: If African-Americans are more likely than whites to suffer from serious mental illness, what about social factors like discrimination?A: We do extensive history taking on every donation to the repository. The team talks to the next of kin. We acquire all records that are available on the deceased—school records, hospital records. We speak to their doctors. It takes weeks. We get a lot of information about the life of the individual.There’s a lot of information now that early childhood toxic stress, however that’s defined, creates increased risk for many, many medical disorders, not just psychiatric disorders. The assumption is that this is changing the [gene expression] in many cells in the body. There’s good reason to believe that individuals who were exposed early in life to tremendous stress, that that leaves a footprint in their genome. We theoretically will be able to look at this, and how that affects gene processing in particular cells in the brain. And then—this is the holy grail—this might lead to some idea of how to rescue [others].Q: Do you feel that you have all these brains but not the resources to study them?A: That is for sure. In Nature Genetics, there was a landmark paper of sequencing from 900 African-American genomes. The take-home message there was mind-boggling: Ten percent of the African-American DNA sequence is missing from the reference sequence of the human genome, which is what’s used in every human study today.We want to catch up with a lot that has already been done in [the brains of people of European-American descent]. We want to do a lot of RNA sequencing. We’re increasingly focused on trying to identify different cells that mediate these risk-specific genetic effects. It’s a huge project.We have African-American brains from prenatal life, from early childhood. Prematurity is much more common in the African-American community. We need to explore this whole question of development in the context of genetic variation.And we have many brains with the diagnosis of schizophrenia, depression, bipolar disorder, drug abuse. There’s a wealth of questions to be asked.Q: What about the money? You’re asking for $5 million from the state of Maryland to help get this off the ground.A: The ask of the state is $2.5 million a year for 2 years. That would jump-start the generation of a lot of deep data, and I think also attract much more interest in this project.Q: Are there unique challenges in running brain genomic studies versus, say, genomic studies of the heart?A: The phenotype [what’s visible] has different levels of analysis. One is the age of the person. Another might be the diagnosis. The third level is the expression, the splicing, the altered regulation of a gene—the expression of a gene in the brain, which is the blueprint of how you build the brain and how the brain responds to the environment. There are so many parts to the brain, [so] many cells in it. We collect living cells from the people whose brains we have, and collaborate with stem cell groups around the country. There are parts of the [brain], like the dura mater [the membrane surrounding the organ], that survive for days after death. We do have living [cell] lines from these brains.There have been huge abuses of the African-American community by the biomedical community. As a result, there is a lot of distrust in the African-American community. Every brain that we get is donated by the next of kin. Getting consent and donation has to be done within 24 hours of the death. We have basically the same frequency of donation—70%—from African-American families [who are approached] that we have from European-American families. That speaks to one of the issues that has dogged this research for a while.Q: It sounds like the partnership with Baltimore clergy leaders is one way to address this. How does that work?A: [The goal is] building trust. It’s to improve possibilities for precision medicine. This train, which has left the station, may be leaving [African-Americans] behind. We convened a group of community leaders of the African-American faith-based community [in Baltimore], led by Alvin Hathaway [principal of the African-American Clergy Medical Research Initiative], an extraordinary man. We had a meeting with 23 leaders. Our hope is to put together an advisory group, which would include community leaders as well as scientists from around the country.last_img

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