Scientific article
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Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness

Published inNature mental health, vol. 3, no. 5, p. 538-547
Publication date2025
First online date2025-04-21
Abstract

Schizophrenia is associated with structural and functional changes in the central nervous system, including the most distal part of it, the retina. However, the question of whether retinal atrophy is present before individuals develop schizophrenia or is a secondary consequence of the disorder remains unanswered. Here we address this question by examining the association between polygenic risk scores for schizophrenia and retinal morphologies in individuals without a schizophrenia diagnosis. We used population data for 34,939 white British and Irish individuals from the UK Biobank. Our robust regression results show that higher polygenic risk scores for schizophrenia were associated with thinner overall maculae, while controlling for confounding factors (b  = -0.17, P  = 0.018). Similarly, we found that greater polygenic risk scores for schizophrenia specific to neuroinflammation gene sets were associated with thinner ganglion cell inner plexiform layers (b  = -0.10, self-contained P  = 0.014, competitive P  = 0.02). These results provide new evidence for genetic factors that could predispose individuals to heightened neuroinflammatory responses. Over time, these responses could contribute to neurodegenerative processes such as retinal thinning.

Keywords
  • Diagnostic markers
  • Genetics research
  • Schizophrenia
Affiliation entities Not a UNIGE publication
Funding
  • NIMH NIH HHS [K23 MH127300]
  • NIMH NIH HHS [R01 MH117646]
  • European Commission - The Delta of Language [101118756]
Citation (ISO format)
RABE, Finn et al. Genetic susceptibility to schizophrenia through neuroinflammatory pathways associated with retinal thinness. In: Nature mental health, 2025, vol. 3, n° 5, p. 538–547. doi: 10.1038/s44220-025-00414-6
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Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/s44220-025-00414-6
Journal ISSN2731-6076
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