Evidence map›Paper›PMID 42778716›Full record

ArticleNature neuroscience2026

Massively parallel assessment of gene regulatory activity at human cortical-structure-associated variants.

Nana Matoba, Jessica C McAfee, Oleh Krupa, Alvaro A Beltran, Jessica L Bell, Brandon D Le, Jordan M Valone, Hyunggyu Min, Gregory E Crawford, Jesse R Raab and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Nana Matoba *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-5329-0134
Jessica C McAfee *Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Oleh KrupaDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Alvaro A BeltranDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-1421-3889
Jessica L BellDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0001-9563-0125
Brandon D LeDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jordan M ValoneDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0003-0338-4436
Hyunggyu MinDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.ORCID http://orcid.org/0000-0002-7944-6130
Gregory E CrawfordDepartment of Pediatrics, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0001-6106-2772
Jesse R RaabDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hyejung WonDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. hyejung_won@med.unc.edu.ORCID http://orcid.org/0000-0003-3651-0566
Jason L SteinDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. jason_stein@med.unc.edu.ORCID http://orcid.org/0000-0003-4829-0513

Funding

Systematic in vivo characterization of disease-associated regulatory variantsUM1HG012003 · NHGRI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael Isaiah Love, KAREN L. MOHLKE · 2021 to 2026
$9.9M
Discovery and validation of genetic variation impacting the gene regulatory landscape during human cortical developmentR01MH122509 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STEIN, JASON LOUIS, WON, HYEJUNG · 2023 to 2025
$1.6M
U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG012003U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH122509
6 · The paper itself

Abstract

Genetic association studies have identified hundreds of largely noncoding loci associated with interindividual differences in the structure of the human cortex, although the specific functional variants contributing to these phenotypes are unknown. Here we implemented a massively parallel reporter assay to measure the regulatory activity of 9,092 cortical-structure-associated variants in human neural progenitor cells at baseline and during Wnt stimulation. We identified 918 variants with regulatory potential from 150 cortical-structure-associated loci (76% of loci studied), of which more than 50% showed allelic effects. Wnt stimulation modified regulatory activity at a subset of loci, revealing condition-dependent enhancers. Massively parallel reporter assay activity was largely induced by Alu elements, suggesting that they contribute to cortical expansion. The region-specific impact of motif-disrupting variants is probably mediated by spatially localized transcription factor expression during development. Together, these results provide a genome-scale functional framework for understanding how noncoding variation influences cortical structure.

Identifiers

PMID42778716

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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.