Evidence map›Paper›PMID 34416157›Full record

ArticleAmerican journal of human genetics2021

Brain-trait-associated variants impact cell-type-specific gene regulation during neurogenesis.

Nil Aygün, Angela L Elwell, Dan Liang, Michael J Lafferty, Kerry E Cheek, Kenan P Courtney, Jessica Mory, Ellie Hadden-Ford, Oleh Krupa, Luis de la Torre-Ubieta and 3 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% of its field
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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Psychiatric Genomics 2025: State of the Art and the Path Forward.The Psychiatric clinics of North America · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. ArXiv · 2024
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Nil AygünDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Angela L ElwellDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Dan LiangDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Michael J LaffertyDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kerry E CheekDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kenan P CourtneyDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jessica MoryDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ellie Hadden-FordDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Oleh KrupaDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Luis de la Torre-UbietaNeurogenetics Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Daniel H GeschwindNeurogenetics Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michael I LoveDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jason L SteinDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: jason_stein@med.unc.edu.
University of North Carolina at Chapel Hill · USUniversity of California, Los Angeles · US

Funding

Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHARLES M PEROU · 1992 to 2026
$59.3M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KITCHEN, SCOTT G · 1991 to 2018
$39.9M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3M
PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Temitope O. Keku · 1985 to 2026
$30.5M
UNC Neuroscience Center Research Cores: MicroscopyP30NS045892 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ZYLKA, MARK J. · 2003 to 2022
$11.5M
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1M
Preclinical CoreP50HD103573 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI GABRIEL S DICHTER · 2020 to 2026
$9.7M
Identification and Characterization of Asymmetrically-Expressed GenesR37MH060233 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2006 to 2014
$5.3M
2/2-Discovery and validation of neuronal enhancers associated with the development of psychiatric disordersU01MH116489 · NIMH · UNIVERSITY OF CHICAGO · PI GAYNOR, SOPHIA, GESCHWIND, DANIEL H · 2018 to 2022
$4.5M
Epigenetic and Transcriptional Dysregulation in Autism Spectrum DisorderR01MH094714 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2011 to 2015
$2.8M
2/3 Integrative Genomic Analysis of Human Brain Development and AutismR01MH110927 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2016 to 2019
$2.7M
The influence of common genetic variation on brain overgrowth pathwaysR01MH120125 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STEIN, JASON LOUIS · 2019 to 2023
$2.5M
NCI NIH HHS P50 CA058223NIAID NIH HHS P30 AI028697NIBIB NIH HHS U54 EB020403NICHD NIH HHS P50 HD103573NIDDK NIH HHS P30 DK034987NIEHS NIH HHS P30 ES010126NIMH NIH HHS R00 MH102357NIMH NIH HHS R01 MH094714NIMH NIH HHS R01 MH110927NIMH NIH HHS R01 MH118349NIMH NIH HHS R01 MH120125NIMH NIH HHS R37 MH060233NIMH NIH HHS U01 MH116489NINDS NIH HHS P30 NS045892
6 · The paper itself

Abstract

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing quantitative trait locus (e/sQTL) analyses is generally performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements active during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs, and allele-specific expression in cultured cells representing two major developmental stages, primary human neural progenitors (n = 85) and their sorted neuronal progeny (n = 74), identifying numerous loci not detected in either bulk developing cortical wall or adult cortex. Using colocalization and genetic imputation via transcriptome-wide association, we uncover cell-type-specific regulatory mechanisms underlying risk for brain-relevant traits that are active during neocortical differentiation. Specifically, we identified a progenitor-specific eQTL for CENPW co-localized with common variant associations for cortical surface area and educational attainment.

Indexed as

Gene Expression Regulation, DevelopmentalQuantitative Trait LociAllelesAlzheimer DiseaseCell DifferentiationChromatinChromosomal Proteins, Non-HistoneChromosome MappingEducational StatusFemaleFetusGenetic Predisposition to DiseaseGenome, HumanGenome-Wide Association StudyHumansMaleCENPW protein, humanChromatinChromosomal Proteins, Non-Histonecell-type specificitycommon genetic variantsexpression/splicing quantitative locigenome-wide association studyneurogenesisneuropsychiatric disorderstranscriptome-wide association study

Identifiers

PMID34416157
PMCPMC8456186
OpenAlexW3194868034

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.