ArticleResearch square2024
Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain.
Biao Zeng, Hui Yang, Prashant N M, Sanan Venkatesh, Deepika Mathur, Pavan Auluck, David A Bennett, Stefano Marenco, Vahram Haroutunian, PsychAD Consortium and 7 more
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In one paragraphArticle in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
17 authors.
Biao ZengCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hui YangCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Prashant N MCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-3548-5637 Sanan VenkateshCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Deepika MathurCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Pavan AuluckHuman Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA.ORCID 0000-0003-4799-7904 David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Stefano MarencoHuman Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA.ORCID 0000-0002-2488-2365 Vahram HaroutunianCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-5860-2512 PsychAD Consortium
Georgios VoloudakisCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-5729-632X Donghoon LeeCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-0453-6059 John F FullardCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-9874-2907 Jaroslav BendlCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-9989-2720 Kiran GirdharCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-5622-042X Gabriel E HoffmanCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-0957-0224 Panos RoussosCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-4640-6239 Funding
Procurement and Characterization of Postmortem Brain TissueZICMH002903 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MARENCO, STEFANO · 2009 to 2025
$56.0MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MConduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MRisk Factors for Cognitive Decline in African-AmericansR01AG022018 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BARNES, LISA L · 2004 to 2025
$18.2MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MUnderstanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8MTO ADMINISTRATIVELY DE-OBLIGATE UNEXPENDED AND EXPIRING FISCAL YEAR 2020 FUNDING IN ACCORDANCE WITH 31 U.S.C. SECTION 1552 (A), IN PREPARATION FOR SEPTEMBER 30, 2025, CLOSING OF THE PERIOD OF AVAILABI75N95019C00049 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM · 2019 to 2025
$11.8MUnderstanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9MIntramural NIH HHS Z01 MH002903Intramural NIH HHS ZIC MH002903NCATS NIH HHS UL1 TR004419NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIA NIH HHS R01 AG078657NIA NIH HHS R01 AG082185NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIDA NIH HHS 75N95019C00049NIH HHS S10 OD026880NIH HHS S10 OD030463NIMH NIH HHS R01 MH125246
6 · The paper itselfAbstract
Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384 donors of diverse ancestries. Through multi-resolution analyses spanning eight major cell classes and 27 subclasses, we identify genetic regulation for 14,258 genes, with 857 showing cell type-specific regulatory effects at the class level and 981 at the subclass level. Colocalization of genetic variants associated with gene regulation and disease traits uncovers novel cell type-specific genes implicated in Alzheimer's disease, schizophrenia, and other disorders, which were not detectable in bulk tissue analyses. Analysis of dynamic genetic regulation at the single nucleus level identifies 2,073 genes with regulatory effects that vary across developmental trajectories, inferred from a broad age range of donors. We also uncover 1,655 genes with
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PMID39711543
PMCPMC11661307
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