Evidence map›Paper›PMID 42069759›Full record

SynthesisNature communications2026

Genetic landscape of adult executive function reveals a cell-type-specific developmental origin.

Md Shafiqur Rahman, Azra Frkatović-Hodžić, Jelle van den Ameele, Steven M Hill, Nathalie Kingston, John R Bradley, Brian D M Tom, Patrick F Chinnery

Abstract readMeta-Analysis
In one paragraph

Synthesis in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Md Shafiqur RahmanDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK. msr52@cam.ac.uk.ORCID http://orcid.org/0000-0003-4068-6775
Azra Frkatović-HodžićGenos Glycoscience Research Laboratory, Zagreb, Croatia.
Jelle van den AmeeleDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
Steven M HillMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-5909-692X
Nathalie KingstonNational Institute for Health and Care Research BioResource, Cambridge, UK.ORCID http://orcid.org/0000-0002-9190-2231
John R BradleyNational Institute for Health and Care Research BioResource, Cambridge, UK.ORCID http://orcid.org/0000-0002-7774-8805
Brian D M TomMRC Biostatistics Unit, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-3335-9322
Patrick F ChinneryDepartment of Clinical Neurosciences, University of Cambridge, Cambridge, UK. pfc25@cam.ac.uk.ORCID http://orcid.org/0000-0002-7065-6617

Funding

LifeArc 10748RCUK | Medical Research Council (MRC) MC_UU_00028/7
6 · The paper itself

Abstract

Executive function is an essential cognitive domain for typical human behavior which is disrupted in neurodevelopmental and neurodegenerative disorders, but little is known about its underlying molecular basis. To address this, we perform genome-wide association studies (GWAS) using three different measures of executive function in UK Biobank (N = 84,238) and NIHR BioResource's Genes and Cognition (N = 9932) study participants, followed by a meta-analysis. The trail-making alphanumeric (TMA) measure is the most heritable phenotype (h²=7-26%), associated with 18 independent loci that exhibit a similar direction of effect in both cohorts. Across these loci, in-silico follow-up implicates 178 genes, of which NT5DC2 and RP11-579E24.2 are independently replicated prior to meta-analysis. TMA is linked to pan-cerebral differences in brain structure, with brain-enriched genes showing a biphasic expression profile from early development through to later life. Our data implicate specific cell types, histone modifications and butyrophilin immunoglobulin family proteins as potential targets for promoting cognitive resilience.

Indexed as

BrainExecutive FunctionAdultCognitionFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypePolymorphism, Single Nucleotide

Identifiers

PMID42069759
PMCPMC13342582

What OpenQuestion holds

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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.