Evidence mapPaperPMID 38438384Full record

ArticleNature communications2024

Genetic architecture of the structural connectome.

Michael Wainberg, Natalie J Forde, Salim Mansour, Isabel Kerrebijn, Sarah E Medland, Colin Hawco, Shreejoy J Tripathy

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
23.0field-weighted citation impact, top 1% 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

31 citing papers in PubMed, 57 citations in OpenAlex.

  1. Genetic pleiotropy differentially linking brain variation to cannabis use and cannabis use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  2. Review
  3. The Cerebellar Connectome.Cerebellum (London, England) · 2026
    Article
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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

7 authors at 4 institutions in 3 countries.

Michael WainbergKrembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada. m.wainberg@utoronto.ca.ORCID http://orcid.org/0000-0001-6061-0239
Natalie J FordeDepartment of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Salim MansourCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Isabel KerrebijnProsserman Centre for Population Health Research, Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
Sarah E MedlandQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-1382-380X
Colin Hawco *Department of Psychiatry, University of Toronto, Toronto, ON, Canada. colin.hawco@camh.ca.
Shreejoy J Tripathy *Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, ON, Canada. shreejoy.tripathy@camh.ca.ORCID http://orcid.org/0000-0002-1007-9061
Centre for Addiction and Mental Health · CARadboud University Nijmegen · NLThe University of Queensland · AUUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Myelinated axons form long-range connections that enable rapid communication between distant brain regions, but how genetics governs the strength and organization of these connections remains unclear. We perform genome-wide association studies of 206 structural connectivity measures derived from diffusion magnetic resonance imaging tractography of 26,333 UK Biobank participants, each representing the density of myelinated connections within or between a pair of cortical networks, subcortical structures or cortical hemispheres. We identify 30 independent genome-wide significant variants after Bonferroni correction for the number of measures studied (126 variants at nominal genome-wide significance) implicating genes involved in myelination (SEMA3A), neurite elongation and guidance (NUAK1, STRN, DPYSL2, EPHA3, SEMA3A, HGF, SHTN1), neural cell proliferation and differentiation (GMNC, CELF4, HGF), neuronal migration (CCDC88C), cytoskeletal organization (CTTNBP2, MAPT, DAAM1, MYO16, PLEC), and brain metal transport (SLC39A8). These variants have four broad patterns of spatial association with structural connectivity: some have disproportionately strong associations with corticothalamic connectivity, interhemispheric connectivity, or both, while others are more spatially diffuse. Structural connectivity measures are highly polygenic, with a median of 9.1 percent of common variants estimated to have non-zero effects on each measure, and exhibited signatures of negative selection. Structural connectivity measures have significant genetic correlations with a variety of neuropsychiatric and cognitive traits, indicating that connectivity-altering variants tend to influence brain health and cognitive function. Heritability is enriched in regions with increased chromatin accessibility in adult oligodendrocytes (as well as microglia, inhibitory neurons and astrocytes) and multiple fetal cell types, suggesting that genetic control of structural connectivity is partially mediated by effects on myelination and early brain development. Our results indicate pervasive, pleiotropic, and spatially structured genetic control of white-matter structural connectivity via diverse neurodevelopmental pathways, and support the relevance of this genetic control to healthy brain function.

Indexed as

ConnectomeAdultBrainGenes, RegulatorGenome-Wide Association StudyHumansIntracellular Signaling Peptides and ProteinsMicrofilament ProteinsProtein KinasesRepressor ProteinsSemaphorin-3ACCDC88C protein, humanIntracellular Signaling Peptides and ProteinsMicrofilament ProteinsNUAK1 protein, humanProtein KinasesRepressor ProteinsSemaphorin-3A

Identifiers

PMID38438384
PMCPMC10912129
OpenAlexW4392377681

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.