Association between polygenic risk for schizophrenia and retinal morphology: A cross-sectional analysis of the United Kingdom Biobank

Psychiatry Research, Год журнала: 2024, Номер 339, С. 116106 - 116106

Опубликована: Июль 26, 2024

We examined the relationship between genetic risk for schizophrenia (SZ), using polygenic scores (PRSs), and retinal morphological alterations. Retinal structural vascular indices derived from optical coherence tomography (OCT) color fundus photography (CFP) PRSs SZ were analyzed in N = 35,024 individuals prospective cohort study, United Kingdom Biobank (UKB). Results indicated that macular ganglion cell-inner plexiform layer (mGC-IPL) thickness was significantly inversely related to PRS SZ, this strongest within higher quintiles independent of potential confounders age. PRS, however, unrelated characteristics, with exception venular tortuosity, other (macular nerve fiber [mRNFL], inner nuclear [INL], cup-to-disc ratio [CDR]). Additionally, association greater reduced mGC-IPL only significant participants 40-49 50-59 age groups, not those 60-69 group. These findings suggest thinning is associated a predisposition may reflect neurodevelopmental and/or neurodegenerative processes inherent SZ. microvasculature alterations, be secondary consequences do appear

Язык: Английский

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Towards interpretable imaging genomics analysis: Methodological developments and applications

Information Fusion, Год журнала: 2023, Номер 102, С. 102032 - 102032

Опубликована: Сен. 19, 2023

Язык: Английский

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Decoding and reconstructing disease relations between dry eye and Depression: A multimodal investigation comprising Meta-analysis, genetic pathways and Mendelian randomization

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Март 1, 2024

The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness mechanisms underlying this association were undetermined.

Язык: Английский

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Genetic susceptibility to schizophrenia through neuroinflammatory pathways is associated with retinal thinning: Findings from the UK-Biobank

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 6, 2024

The human retina is part of the central nervous system and can be easily non-invasively imaged with optical coherence tomography. While imaging may provide insights on system-related disorders such as schizophrenia, a typical challenge are confounders often present in schizophrenia which negatively impact retinal health. Here, we therefore aimed to investigate changes context common genetic variations conveying risk measured by polygenic scores. We used population data from UK Biobank, including White British Irish individuals without diagnosed estimated score for based newest genome-wide association study (PGC release 2022). hypothesized that greater susceptibility associated thinning, especially within macula. To gain additional mechanistic insights, conducted pathway-specific associations analyses, focusing gene pathways related schizophrenia. Of 65484 recruited, 48208 participants available matching imaging-genetic were included analysis whom 22427 (53.48%) female 25781 (46.52%) male. Our robust principal component regression results showed scores thinning while controlling confounding factors (b = −0.03, p 0.007, pFWER 0.01). Similarly, found specific neuroinflammation sets revealed significant self-contained 0.041 (reflecting level association), competitive 0.05 enrichment)). These go beyond previous studies suggesting relationship between manifested phenotypes. They indicate mirror reflecting complexities alterations observed connected an inherent predisposition neurodegenerative aspects condition. also suggest potential involvement neuroinflammatory pathway, indications overlap findings further this pathway high could contribute through acute-phase proteins structural retina.

Язык: Английский

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Genetic network analysis indicate that individuals affected by neurodevelopmental conditions have genetic variations associated with ophthalmologic alterations: A critical review of literature

Gene, Год журнала: 2024, Номер 908, С. 148246 - 148246

Опубликована: Фев. 6, 2024

Язык: Английский

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Multi-organ imaging-derived polygenic indexes for brain and body health

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 20, 2023

The UK Biobank (UKB) imaging project is a crucial resource for biomedical research, but limited to 100,000 participants due cost and accessibility barriers. Here we used genetic data predict heritable imaging-derived phenotypes (IDPs) larger cohort. We developed evaluated 4,375 IDP scores (IGS) derived from UKB brain body images. When applied who were not imaged, IGS revealed links numerous stratified at increased risk both somatic diseases. For example, identified individuals higher Alzheimer's disease multiple sclerosis, offering additional insights beyond traditional polygenic of these independent external cohorts, also those high in the All Us Research Program Disease Neuroimaging Initiative study. Our results demonstrate that, while cohort largely healthy may be most enriched management, it holds immense potential stratifying various diseases broader cohorts.

Язык: Английский

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Autoencoder-based phenotyping of ophthalmic images highlights genetic loci influencing retinal morphology and provides informative biomarkers

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июнь 20, 2023

ABSTRACT Genome-wide association studies (GWAS) have been remarkably successful in identifying associations between genetic variation and imaging-derived phenotypes. To date, the main focus of these analyses has established, clinically-used imaging features. Here, we sought to investigate if deep learning approaches can help detect more nuanced patterns image variability. this end, used an autoencoder represent retinal optical coherence tomography (OCT) images from 31,135 UK Biobank participants. For each study subject, obtained a 64-dimensional vector representing features structure. GWAS autoencoder-derived parameters identified 118 statistically significant loci; 17 also reached genome-wide significance replication analysis that included 10,409 volunteers. These loci encompassed variants previously linked with thickness measurements, ophthalmic disorders and/or neurodegenerative conditions (including dementia). Notably, generated phenotypes were found contribute predictive models for glaucoma cardiovascular disorders. Overall, demonstrate self-supervised phenotyping OCT enhances discoverability factors influencing morphology provides epidemiologically informative biomarkers.

Язык: Английский

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Overlap between ophthalmology and psychiatry – A narrative review focused on congenital and inherited conditions

Psychiatry Research, Год журнала: 2023, Номер 331, С. 115629 - 115629

Опубликована: Ноя. 25, 2023

Язык: Английский

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Systematic dissection of pleiotropic loci and critical regulons in exhibitory neurons and microglia relevant to neuropsychiatric and ocular diseases

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 12, 2024

Background: Single-cell multimodal techniques have advanced the functional elucidation of disease-relevant loci identified in genome-wide association studies (GWASs). However, interpretation these variants remains challenging. It is still unclear how modulate core gene-regulatory networks specific cell types to influence eye-and brain-related diseases. Methods: We developed a computational framework integrate bulk and single-cell multiomic (scRNA-seq scATAC-seq) profiles with GWAS summary statistics for identifying critical transcription factor (TF)-regulatory regulons through which genetic eight neuropsychiatric five ocular Various methods were utilized uncover pleiotropic loci, risk genes, key pathways Results: Our analysis revealed latent factors explaining 61.7% variances across 13 eye brain diseases, showing diverse correlational patterns among conditions. We 45 91 candidate genes contributing disease risk. Integration sequencing data implicated excitatory neurons microglia eye-brain connections. Network-based polygenic enrichment 15 exhibitory neurons, including BCL11A, STAT4, GLS1, 16 microglia, such as SPI1, FOXP2, MEF2C. Exhibitory neuron-specific functionally involved axon guidance synaptic activity, while microglia-specific related immune response activation. Conclusions: study reinforces link between psychiatric diseases provides biological insights into potential regulatory mechanisms implications future therapeutic development.

Язык: Английский

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Guest editors' introduction: The retina as a biomarker in neuropsychiatric disorders

Biomarkers in Neuropsychiatry, Год журнала: 2024, Номер 10, С. 100100 - 100100

Опубликована: Май 31, 2024

Язык: Английский

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