Genome-Wide Association Study Finds Multiple Loci Associated with Intraocular Pressure in HS Rats DOI Creative Commons
Samuel Fowler, Tengfei Wang, Daniel Munro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 17, 2022

Abstract Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the basis may lead to better understanding molecular mechanisms POAG. The goal this study was identify loci involved in regulating using outbred heterogeneous stock (HS) rats. HS rats are multigenerational population derived from eight inbred strains that have been fully sequenced. This ideal genome-wide association studies (GWASs) owing accumulated recombinations among well-defined haplotypes, relatively high allele frequencies, accessibility large collection tissue samples, allelic effect size compared human studies. Both male female (N=1,812) were used study. Genotyping-by-sequencing obtain ~3.5 million single nucleotide polymorphisms (SNP) each individual. SNP heritability 0.32, which agrees with other We performed GWAS phenotype linear mixed model permutation determine significance threshold. identified three significant on chromosomes 1, 5, 16. Next, we sequenced mRNA 51 whole eye samples find cis-eQTLs aid identification candidate genes. report 5 genes within those loci: Tyr , Ctsc Plekhf2 Ndufaf6 Angpt2 . previously implicated IOP-related conditions. represent novel findings provide new insight into IOP. highlights efficacy investigating genetics elevated identifying potential future functional testing. Contribution field statement Glaucoma leading cause irreversible blindness worldwide. Intraocular only known modifiable factor. describes results (GWAS) identifies regulation. To our knowledge, first rat model. Identifying provides factors humans pharmacological targets advantageous studying natural variations IOP, controlling exposures, providing easier access can be phenotyping gene expression

Language: Английский

Primary Open Angle Glaucoma Prevalence in Europe: A Systematic Review and Meta-Analysis DOI
Gabriele Gallo Afflitto, Francesco Aiello, Massimo Cesareo

et al.

Journal of Glaucoma, Journal Year: 2022, Volume and Issue: 31(10), P. 783 - 788

Published: Aug. 9, 2022

Purpose: This study aimed to evaluate the prevalence of POAG in Europe. Methods: Two authors independently conducted a systematic literature search on PubMed/MedLine, Web Science, and Google Scholar identify papers analyzing European countries. After removal duplicates, title abstract screening, full-text analysis, data from selected articles were entered an Excel spreadsheet. We performed risk bias assessment using Joanna Briggs Institute Prevalence Critical Appraisal Tool meta-analysis R software (version 1.4.1106). Results: retrieved 9348 eligible initial electronic included 10 them qualitative quantitative analyses. A total 26,993 patients this (11,927 male 14,556 female). identified 755 cases (397 348 female), with pooled estimate Europe 2.60% (95% confidence interval: 1.90%–3.56%). Increasing odds for related increasing age some geographic differences disease distribution continent identified. Statistically significant sex-related rate not observed cohort. Conclusion: is neurodegenerative that affects large proportion older population. In future, expected grow because progressive aging populations Western Future high-quality epidemiological studies evaluation rates are warranted.

Language: Английский

Citations

29
Establishing the Normative Data Set Necessary for Imaging-Based Childhood Uveitis Surveillance: A Cross-Sectional Study DOI Creative Commons
Ameenat Lola Solebo, Alice Bellchambers, Salomey Kellett

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(1), P. 9 - 9

Published: Jan. 3, 2024

Purpose: Anterior segment optical coherence tomography (AS-OCT) is an emerging diagnostic and monitoring tool for anterior uveitis. We investigated AS-OCT findings in the eyes of a large, diverse population children free uveitis to establish its potential "rule out" accurately those without disease. Methods: In this cross-sectional observational study, image acquisition was performed with swept source (Heidelberg Anterion), using protocol 13 B-scans per volume, from 217 (434 eyes) aged 5 15 years, analysis acquired images (identification apparent inflammatory cells, or "cell events") by multiple graders. Outcomes interest were median maximum cell event count (MEDCC, MAXCC) B-scan each eye total (TCC) volume scan. Results: At least one detected scans 76% (329/434) 87% (189/217). The number (MAXCC) scan ranged 0 6 (median, 2). There strong positive association between increasing age (years) events within following adjustment gender iris color (adjusted regression coefficient TCC 0.5; P < 0.0001; 95% confidence interval, 0.4–0.7). Conclusions: Our demonstrate that cells are detectable on apparently healthy furthermore suggest early life developmental changes blood–iris barrier stability merit further exploration. provide foundation normative data set necessary establishing clinical utility surveillance diseases.

Language: Английский

Citations

6
Genome-wide association analyses identify distinct genetic architectures for age-related macular degeneration across ancestries DOI
Bryan R. Gorman, Georgios Voloudakis, Robert P. Igo

et al.

Nature Genetics, Journal Year: 2024, Volume and Issue: 56(12), P. 2659 - 2671

Published: Dec. 1, 2024

Language: Английский

Citations

3
Applications of Genomics and Transcriptomics in Precision Medicine for Myopia Control or Prevention DOI Creative Commons
Liqin Jiang,

Dong Xuan Goh,

James Koh

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(3), P. 494 - 494

Published: March 7, 2023

Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics transcriptomics myopia crucial delineate disease pathways provide valuable insights for design precise effective therapeutics. A strong understanding altered biochemical underlying pathogenesis leading may facilitate early diagnosis myopia, ultimately development more preventive therapeutic measures. In this review, we summarize current data about in human animal models. We also discuss potential applicability these findings precision medicine treatment.

Language: Английский

Citations

8
Genome-wide association study finds multiple loci associated with intraocular pressure in HS rats DOI Creative Commons
Samuel Fowler, Tengfei Wang, Daniel Munro

et al.

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 30, 2023

Elevated intraocular pressure (IOP) is influenced by environmental and genetic factors. Increased IOP a major risk factor for most types of glaucoma, including primary open angle glaucoma (POAG). Investigating the basis may lead to better understanding molecular mechanisms POAG. The goal this study was identify loci involved in regulating using outbred heterogeneous stock (HS) rats. HS rats are multigenerational population derived from eight inbred strains that have been fully sequenced. This ideal genome-wide association (GWAS) owing accumulated recombinations among well-defined haplotypes, relatively high allele frequencies, accessibility large collection tissue samples, allelic effect size compared human studies. Both male female (N = 1,812) were used study. Genotyping-by-sequencing obtain ∼3.5 million single nucleotide polymorphisms (SNP) each individual. SNP heritability 0.32, which agrees with other We performed GWAS phenotype linear mixed model permutation determine significance threshold. identified three significant on chromosomes 1, 5, 16. Next, we sequenced mRNA 51 whole eye samples find cis-eQTLs aid identification candidate genes. report 5 genes within those loci: Tyr, Ctsc, Plekhf2, Ndufaf6 Angpt2. Angpt2 previously implicated IOP-related conditions. Ctsc Plekhf2 represent novel findings provide new insight into IOP. highlights efficacy investigating genetics elevated identifying potential future functional testing.

Language: Английский

Citations

7
Genetic Basis of Pigment Dispersion Syndrome and Pigmentary Glaucoma: An Update and Functional Insights DOI Open Access
Shi Song Rong, Xinting Yu, Janey L. Wiggs

et al.

Genes, Journal Year: 2024, Volume and Issue: 15(2), P. 142 - 142

Published: Jan. 23, 2024

Pigment Dispersion Syndrome (PDS) and Pigmentary Glaucoma (PG) comprise a spectrum of ocular disorders characterized by iris pigment dispersion trabecular meshwork changes, resulting in increased intraocular pressure potential glaucomatous optic neuropathy. This review summarizes recent progress PDS/PG genetics including rare pathogenic protein coding alterations (PMEL) susceptibility loci identified from genome-wide association studies (GSAP GRM5/TYR). Areas for future research are also identified, especially the development efficient model systems. While substantial strides have been made understanding PDS/PG, our identifies key gaps outlines directions necessary further advancing this important field genetics.

Language: Английский

Citations

2
Distinctive cross-ancestry genetic architecture for age-related macular degeneration DOI Open Access
Bryan R. Gorman, Georgios Voloudakis, Robert P. Igo

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Aug. 21, 2022

Abstract To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles African and Hispanic/Latino ancestries, remains largely unknown lower lifetime prevalence. We combined clinical data the Million Veteran Program with five other cohorts conduct first multi-ancestry genome-wide association study discovered 63 loci (30 novel). observe marked cross-ancestry heterogeneity at major loci, especially African-ancestry which demonstrate primary signal Major Histocompatibility Complex Class II haplotype reduced established CFH ARMS2/HTRA1 loci. Broadening efforts include ancestrally-distinct helped uncover genes pathways boost an ancestry-dependent manner, are potential targets for corrective therapies. One Sentence Summary robing electronic health record genomics unearths novel paths degeneration.

Language: Английский

Citations

11
Pigment dispersion syndrome and pigmentary glaucoma: overview and racial disparities DOI

Ruiqi Pang,

Siloka Arthur Labisi,

Ningli Wang

et al.

Graefe s Archive for Clinical and Experimental Ophthalmology, Journal Year: 2022, Volume and Issue: 261(3), P. 601 - 614

Published: Sept. 10, 2022

Language: Английский

Citations

9
Beyond the optic nerve: Genetics, diagnosis, and promising therapies for glaucoma DOI

Meenakshi Kaushik,

Prabhakar Tiwari,

Tanuj Dada

et al.

Gene, Journal Year: 2023, Volume and Issue: 894, P. 147983 - 147983

Published: Nov. 10, 2023

Language: Английский

Citations

5
Identification of hub genes for glaucoma: a study based on bioinformatics analysis and experimental verification DOI Creative Commons
Ruiling Xie,

Yuxin Xu

International Journal of Ophthalmology, Journal Year: 2023, Volume and Issue: 16(7), P. 1015 - 1025

Published: June 28, 2023

To explore hub genes for glaucoma based on bioinformatics analysis and an experimental model verification.In the Gene Expression Omnibus (GEO) database, GSE25812 GSE26299 datasets were selected to analyze differentially expressed (DEGs) by GEO2R tool. Through analysis, 9 identified. Receiver operating characteristic (ROC) curves principal component (PCA) performed verify whether gene can distinguish from normal eyes. The mouse of was constructed, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) assay detect expression levels in glaucoma.There 128 overlapping DEGs datasets, mainly involved intracellular signalling, cell adhesion molecules Ras signalling pathway. A total screened out, including GNAL, BGN, ETS2, FCGP4, MAPK10, MMP15, STAT1, TSPAN8, VCAM1. area under curve (AUC) values greater than 0.8. PC1 axle could provide a 70.5% interpretation rate In ocular tissues mice model, FCGR4, VCAM1 increased, while MMP15 decreased.Nine are identified, which may new biomarkers therapeutic targets glaucoma.

Language: Английский

Citations

4