Identification of Potential Drug Targets for Myopia Through Mendelian Randomization.
Invest Ophthalmol Vis Sci
; 65(10): 13, 2024 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-39110588
ABSTRACT
Purpose:
The purpose of this study was to identify potential drug targets for myopia and explore underlying mechanisms.Methods:
Mendelian randomization (MR) was implemented to assess the effect of 2684 pharmacologically targetable genes in the blood and retina on the risk of myopia from a genomewide association study (GWAS) for age-at-onset of spectacle wearing-inferred mean spherical equivalent (MSE; discovery cohort, N = 287,448, European), which was further validated in a GWAS for autorefraction-measured MSE (replication cohort, N = 95,619, European). The reliability of the identified significant potential targets was strengthened by colocalization analysis. Additionally, enrichment analysis, protein-protein interaction network, and molecular docking were performed to explore the functional roles and the druggability of these targets.Results:
This systematic drug target identification has unveiled 6 putative genetically causal targets for myopia-CD34, CD55, Wnt3, LCAT, BTN3A1, and TSSK6-each backed by colocalization evidence in adult blood eQTL datasets. Functional analysis found that dopaminergic neuron differentiation, cell adhesion, Wnt signaling pathway, and plasma lipoprotein-associated pathways may be involved in myopia pathogenesis. Finally, drug prediction and molecular docking corroborated the pharmacological value of these targets with LCAT demonstrating the strongest binding affinity.Conclusions:
Our study not only opens new avenues for the development of therapeutic interventions for myopia but may also help to understand the underlying mechanisms of myopia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
/
Análise da Randomização Mendeliana
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Miopia
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article