Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders

JAMA Psychiatry, Journal Year: 2025, Volume and Issue: 82(3), P. 285 - 285

Published: Jan. 8, 2025

Importance As an accessible part of the central nervous system, retina provides a unique window to study pathophysiological mechanisms brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric neurological disorders, but it remains largely unclear which specific cell types biological are involved. Objective To determine whether affected by genomic risk for explore through converges these types. Design, Setting, Participants This genetic association combined findings from genome-wide schizophrenia, bipolar disorder, major depressive multiple sclerosis, Parkinson disease, Alzheimer stroke with single-cell transcriptomic datasets humans, macaques, mice. identify susceptible types, Multi-Marker Analysis Genomic Annotation (MAGMA) cell-type enrichment analyses were applied subsequent pathway performed. The cellular top hits translated structural level using optical coherence tomography (acquired between 2009 2010) genotyping data large population-based UK Biobank cohort study. Data analysis was conducted 2022 2024. Main Outcomes Measures Cell type–specific loading disorder traits gene expression profiles cells. Results Expression amacrine cells (interneurons within retina) robustly enriched schizophrenia mammalian species different developmental stages. primarily driven genes involved synapse biology. Moreover, immune populations sclerosis risk. No consistent associations found or stroke. On level, higher polygenic associated thinning ganglion inner plexiform layer, contains dendrites synaptic connections (B, −0.09; 95% CI, −0.16 −0.03; P = .007; n 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher increased thickness nerve fiber layer 0.06; 0.02 0.10; 371; 57.51 843 [54.56%]). Conclusions Relevance novel insights into underpinnings highlights as potential proxy pathology schizophrenia.

Language: Английский

Genetic analysis of retinal cell types reveals synaptic pathology in schizophrenia

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 12, 2024

Importance: As an accessible part of the central nervous system, retina provides a unique window to study pathophysiological mechanisms brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric neurological disorders. However, it remains largely unclear whether primary disease within contribute observed which specific cell types biological are involved. Objective: To determine affected by genomic risk for explore through converges these types. Design, Setting, Participants: In this study, we combined findings from genome-wide association schizophrenia, bipolar disorder, major depressive multiple sclerosis, Parkinson disease, Alzheimer stroke with single-cell transcriptomic data sets humans, macaques, mice. identify susceptible types, applied MAGMA type enrichment analyses performed subsequent pathway analyses. Furthermore, translated cellular top hit structural level using optical coherence tomography genotyping large population-based UK Biobank cohort (n = 36,349). Main Outcomes Measures: Cell type-specific genetic loading disorder traits gene expression profiles cells. Results: Amacrine cells (interneurons retina) were robustly enriched schizophrenia mammalian species different developmental stages. This was primarily driven genes involved synapse biology. On level, higher polygenic associated thinning ganglion cell-inner plexiform layer, contains dendrites synaptic connections amacrine Moreover, immune populations sclerosis risk. No consistent associations found or stroke. Conclusions Relevance: novel insights into underpinnings highlights as potential proxy pathology schizophrenia.

Language: Английский