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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2024-06-11T00:00:00-04:00" class="date-display-single">June 11, 2024</span></p><div class='syndicate'><h1>Scientists map gene-regulating networks in human brain </h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Researchers created massive, advanced maps of the complex networks that regulate gene function in the brains of people with and without mental disorders.</li>
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<li>The findings offer new insights into how gene activities affect the brain, which could lead to improved treatments for mental health conditions.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Illustration of DNA molecule with connecting networks and swirls all around it.">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=id74W9vo&timestamp=1718122287 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=x6S-GMjv&timestamp=1718122287 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=AqNi3luV&timestamp=1718122287 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=-sPgjbxE&timestamp=1718122287 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=uo2jTe75&timestamp=1718122287 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2024/20240611-genese-brain.jpg?itok=x6S-GMjv&timestamp=1718122287" alt="Illustration of DNA molecule with connecting networks and swirls all around it." title="Illustration of DNA molecule with connecting networks and swirls all around it." />
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</picture><span class="caption">Most of the human genome doesn’t contain protein-coding genes, but rather the complicated network of DNA sequences that regulate our genes. </span><span class="credit">Peshkova / Shutterstock</span></div>
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</div><p>Less than 2% of the human genome is made up of genes that code for proteins. The remaining 98% includes DNA segments that help to direct the activity of those genes. These regulatory sequences can have a powerful impact on our health. But their activities and functions in the human brain and their role in mental health remain poorly understood.</p>
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||
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||
<p>To learn more, NIH launched a multi-site initiative called the PsychENCODE Consortium in 2015. It is designed to uncover the details of how genes are regulated and expressed (turned on or off) in the brain. An initial set of results <a href="https://www.nih.gov/news-events/nih-research-matters/revealing-gene-regulation-brain">reported five years ago</a> uncovered new details about the regulatory networks that can affect the risk of several psychiatric disorders.</p>
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||
<p>The consortium’s most recent set of findings used advanced tools and techniques to expand on those earlier results. Researchers had access to postmortem brain tissue from more than 2,500 donors. They were of various ages. Some had mental disorders such as schizophrenia or bipolar disorder while others did not. This variety allowed researchers to map gene regulation networks across different cell types and stages of life, health, and dysfunction. Results were reported in more than a dozen research papers published between May 23 and 29, 2024, in <em>Science</em> and related journals.</p>
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||
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||
<p>One study combined high-throughput experiments and machine learning to assess the activity of DNA regions that may affect gene expression in developing human brain cells. Among the findings, the analysis identified more than 46,000 gene regulatory elements called enhancers. These DNA sequences affect the expression of specific genes. The team also showed that more than 160 variants previously linked to psychiatric disorders alter gene regulation. The tools and techniques developed for this study can now be used by researchers to rapidly and accurately predict how noncoding regions of DNA can affect gene regulation in developing brain cells. This has a variety of uses, including supporting advances in potential therapies for psychiatric disorders.</p>
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||
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||
<p>Another study assessed gene regulation in different types of brain cells. The 388 adult donors included people with schizophrenia, bipolar disorder, autism spectrum disorder, post-traumatic stress disorder, and Alzheimer’s disease. Others had not been diagnosed with a mental disorder. The researchers performed single-cell experiments on more than 2.8 million brain cells. They identified more than half a million regulatory elements specific to 28 different cell types. Overall, they identified more than 1.4 million regions associated with variation in gene expression. Such regions are called expression quantitative trait loci, or eQTLs. This enabled them to determine genes and drug targets for different disorders. The team also created a scientific resource called BrainSCOPE to provide other scientists with their raw data files and other resources.</p>
|
||
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||
<p>These studies detailed many new insights into schizophrenia, autism spectrum disorders, and other mental health disorders. Additional papers described new methods and tools that other research teams can now use to analyze the extensive data produced by the effort. This includes an interactive web-based platform called PsychSCREEN to help researchers explore the new data.</p>
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||
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||
<p>“These groundbreaking findings advance our understanding of where, how, and when genetic risk contributes to mental disorders such as schizophrenia, post-traumatic stress disorder, and depression,” says Dr. Joshua A. Gordon, director of NIH’s National Institute of Mental Health. “Moreover, the critical resources, shared freely, will help researchers pinpoint genetic variants that are likely to play a causal role in mental illnesses and identify potential molecular targets for new therapeutics.”</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/study-reveals-unseen-details-human-brain-structure" target="_top">Unseen Details of Human Brain Structure Revealed </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/scientists-build-largest-maps-date-cells-human-brain" target="_top">Scientists Build Largest Maps to Date of Cells in Human Brain </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/revealing-gene-regulation-brain" target="_top">Revealing Gene Regulation in the Brain </a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/mental-disorders-may-share-molecular-origins" target="_top">Mental Disorders May Share Molecular Origins </a></li><li><a href="https://www.nimhgenetics.org/resources/psychencode" target="_top">PsychENCODE Consortium</a></li><li><a href="https://www.genome.gov/about-genomics/fact-sheets/Transcriptome-Fact-Sheet" target="_top">What Is a Transcriptome?</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.science.org/collections/psychencode2">PSYCHENCODE2 Collection</a>.
|
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<a href="https://pubmed.ncbi.nlm.nih.gov/38781384/">Decoding the Brain.</a> Nusinovich Y. <em>Science. </em>2024 May 24;384(6698):858-859. doi: 10.1126/science.adp9365. Epub 2024 May 23. PMID: 38781384.
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<a href="https://pubmed.ncbi.nlm.nih.gov/38781390">Massively parallel characterization of regulatory elements in the developing human cortex.</a> Deng C, Whalen S, Steyert M, Ziffra R, Przytycki PF, Inoue F, Pereira DA, Capauto D, Norton S, Vaccarino FM; Pollen AA, Nowakowski TJ, Ahituv N, Pollard KS; PsychENCODE Consortium. <em>Science</em>. 2024 May 24;384(6698):eadh0559. doi: 10.1126/science.adh0559. Epub 2024 May 24. PMID: 38781390.
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<a href="https://pubmed.ncbi.nlm.nih.gov/38781369/">Single-cell genomics and regulatory networks for 388 human brains.</a> Emani PS, Liu JJ, Clarke D, Jensen M, Warrell J, Gupta C, Meng R, Lee CY, Xu S, Dursun C, Lou S, Chen Y, Chu Z, Galeev T, Hwang A, Li Y, Ni P, Zhou X; PsychENCODE Consortium‡; Bakken TE, Bendl J, Bicks L, Chatterjee T, Cheng L, Cheng Y, Dai Y, Duan Z, Flaherty M, Fullard JF, Gancz M, Garrido-Martín D, Gaynor-Gillett S, Grundman J, Hawken N, Henry E, Hoffman GE, Huang A, Jiang Y, Jin T, Jorstad NL, Kawaguchi R, Khullar S, Liu J, Liu J, Liu S, Ma S, Margolis M, Mazariegos S, Moore J, Moran JR, Nguyen E, Phalke N, Pjanic M, Pratt H, Quintero D, Rajagopalan AS, Riesenmy TR, Shedd N, Shi M, Spector M, Terwilliger R, Travaglini KJ, Wamsley B, Wang G, Xia Y, Xiao S, Yang AC, Zheng S, Gandal MJ, Lee D, Lein ES, Roussos P, Sestan N, Weng Z, White KP, Won H, Girgenti MJ, Zhang J, Wang D, Geschwind D, Gerstein M; PsychENCODE Consortium. <em>Science.</em> 2024 May 24;384(6698):eadi5199. doi: 10.1126/science.adi5199. Epub 2024 May 24. PMID: 38781369.
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<a href="https://pubmed.ncbi.nlm.nih.gov/38781344/">Using a comprehensive atlas and predictive models to reveal the complexity and evolution of brain-active regulatory elements.</a> Pratt HE, Andrews G, Shedd N, Phalke N, Li T, Pampari A, Jensen M, Wen C, Consortium P, Gandal MJ, Geschwind DH, Gerstein M, Moore J, Kundaje A, Colubri A, Weng Z. <em>Sci Adv.</em> 2024 May 24;10(21):eadj4452. doi: 10.1126/sciadv.adj4452. Epub 2024 May 23. PMID: 38781344
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<a href="https://pubmed.ncbi.nlm.nih.gov/38781368/">Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain. </a>Wen C, Margolis M, Dai R, Zhang P, Przytycki PF, Vo DD, Bhattacharya A, Matoba N, Tang M, Jiao C, Kim M, Tsai E, Hoh C, Aygün N, Walker RL, Chatzinakos C, Clarke D, Pratt H; PsychENCODE Consortium†; Peters MA, Gerstein M, Daskalakis NP, Weng Z, Jaffe AE, Kleinman JE, Hyde TM, Weinberger DR, Bray NJ, Sestan N, Geschwind DH, Roeder K, Gusev A, Pasaniuc B, Stein JL, Love MI, Pollard KS, Liu C, Gandal MJ; PsychENCODE Consortium. <em>Science</em>. 2024 May 24;384(6698):eadh0829. doi: 10.1126/science.adh0829. Epub 2024 May 24. PMID: 38781368.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Mental Health (NIMH), National Human Genome Research Institute (NHGRI), National Institute on Aging (NIA), National Institute on Drug Abuse (NIDA), and National Institute of Neurological Disorders and Stroke (NINDS); New York Stem Cell Foundation; Simons Foundation; Coordination for the Improvement of Higher Education Personnel (CAPES/Brazil) Department of Veterans Affairs; American Foundation for Suicide Prevention; State of Connecticut Department of Mental Health and Addiction Services.</p>
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