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Genetic Architecture of Perivascular Space Morphology in the Pediatric Brain

Jessica Morrel1,2, Hedyeh Ahmadi1, Carinna Torgerson1,2

  • 1Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Biorxiv : the Preprint Server for Biology
|June 4, 2026
PubMed

Insights

Genetic factors influence childhood perivascular space (PVS) morphology, revealing developmental and regional differences. These findings in children aged 9-10 suggest early genetic architecture may impact glymphatic system maturation.

Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Biology

Background:

  • Perivascular spaces (PVS) are crucial for brain homeostasis, facilitating metabolite delivery and waste clearance.
  • The genetic underpinnings of PVS morphology during childhood are largely unknown.
  • Understanding childhood PVS development is key to comprehending brain health trajectories.

Purpose of the Study:

  • To investigate the genetic determinants of PVS morphology in children.
  • To examine associations between single nucleotide polymorphisms (SNPs) and PVS structure in early development.
  • To identify specific genes and pathways influencing childhood PVS morphology.

Main Methods:

  • Utilized cross-sectional data from the Adolescent Brain Cognitive Development Study (N=6,600; ages 9-10).
  • Integrated genomics with 3T structural magnetic resonance imaging (MRI).
  • Employed linear mixed-effects models to analyze associations between 45 SNPs and PVS count/volume fraction across multiple brain regions and subregions.

Main Results:

  • Fifteen SNPs showed significant associations with PVS morphology at the macroregion level, primarily affecting volume fraction.
  • Twenty-one SNPs were associated with PVS morphology at the subregion level, highlighting localized genetic influences.
  • Variants near SLC13A3 demonstrated the most prominent associations with PVS volume fraction; other implicated pathways include Wnt signaling and glymphatic function.

Conclusions:

  • Genetic influences on PVS morphology are detectable in childhood, exhibiting significant regional and developmental specificity.
  • Subregion-level analysis revealed genetic associations missed by broader regional averaging.
  • Childhood PVS genetic architecture may predict glymphatic maturation and subsequent cognitive outcomes, warranting longitudinal investigation.
Abstract

Keywords:
ABCDAdolescent Brain Cognitive Development StudyChildhoodPVSSNPs

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