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Beyond volume: Unraveling the genetics of human brain geometry.
Sci. Adv. 11:eadr1644 (2025)
Brain geometry affects brain function. A quantitative encoding of form is provided by the Laplace-Beltrami operator's spectrum of eigenvalues (LBS). We examined LBS genetics of 22 subcortical brain structures and cerebellum in 19,862 healthy White-British UK Biobank participants by multivariate genome-wide association study on the first 49 eigenvalues each. Controlling for surface and volume, we identified 80 unique variants influencing the shapes of one or several structures, with the highest yield (37 variants) for brain stem. The previously known influence of several of these loci on basic morphology, such as volume, is thus shown to also influence complex shape. Known associations of observed loci with blood pressure, neurodegeneration, alcohol consumption, and mental disorders hint at preclinical stages of these conditions potentially mediating the genetic effect on brain morphology. Significant correlations between LBS of several brain structures and the polygenic risks of hypertension, ischemic stroke, and schizophrenia evince brain shapes as early biomarkers.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Single-nucleotide Polymorphisms; Genome-wide Association; Surface-based Analysis; Alzheimers-disease; Tau Gene; Supranuclear; Haplotype; Shape; Segmentation; Architecture
Language
english
Publication Year
2025
HGF-reported in Year
2025
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
Journal
Science Advances
Quellenangaben
Volume: 11,
Issue: 24,
Article Number: eadr1644
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
Washington, DC [u.a.]
Reviewing status
Peer reviewed
Institute(s)
Institute of Neurogenomics (ING)
Helmholtz AI - FZJ (HAI - FZJ)
Helmholtz AI - FZJ (HAI - FZJ)
POF-Topic(s)
30205 - Bioengineering and Digital Health
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-503200-001
Grants
Helmholtz Imaging grant (BrainShapes)
Helmholtz Imaging grant (NimRLS)
Helmholtz Imaging grant (NimRLS)
WOS ID
001508114400004
Scopus ID
105008515661
PubMed ID
40512868
Erfassungsdatum
2025-06-17