Evidence map›Paper›PMID 42778721›Full record

ArticleNature genetics2026

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

Abstract read
PubMed Publisher
In one paragraph

Article in Nature genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors 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 http://orcid.org/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 http://orcid.org/0000-0003-4799-7904
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Stefano MarencoHuman Brain Collection Core, National Institute of Mental Health-Intramural Research Program, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2488-2365
Vahram HaroutunianCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5860-2512
PsychAD Consortium
Georgios VoloudakisCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-5729-632X
Donghoon LeeCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0003-0453-6059
John F FullardCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9874-2907
Jaroslav BendlCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9989-2720
Kiran GirdharCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-5622-042X
Gabriel E Hoffman *Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. gabriel.hoffman@mssm.edu.ORCID http://orcid.org/0000-0002-0957-0224
Panos Roussos *Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu.ORCID http://orcid.org/0000-0002-4640-6239

Funding

Understanding 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
$11.8M
TO 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
$11.8M
Understanding 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
$9.9M
Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0M
Identifying genetically driven gene dysregulation in Alzheimer's disease and related dementias using statistical data integrationR01AG078657 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Georgios Voloudakis · 2023 to 2026
$2.7M
U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01AG067025, R01AG082185, R01AG065582, R01MH125246, R01AG050986, R01AG095776, U24AG087563U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) 75N95019C00049U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH002903U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) P30AG72975U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG065582U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG067025U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG078657U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG15819U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG17917U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG22018U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01MH125246U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG46152U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) U01AG61356
6 · The paper itself

Abstract

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. Here we present 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 981 showing cell type-specific regulatory effects at the class level and 857 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 that 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 trans-regulatory effects, revealing distal regulation of gene expression. This high-resolution atlas provides insight into the cell type-specific regulatory architecture of the human brain, and offers novel mechanistic targets for understanding the genetic basis of neuropsychiatric and neurodegenerative diseases.

Indexed as

BrainCell NucleusGene Expression RegulationPrefrontal CortexAlzheimer DiseaseGenetic Predisposition to DiseaseHumansOrgan SpecificitySchizophreniaSingle-Cell Gene Expression Analysis

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.