Work

Multi-omics Mendelian randomisation reveals distinct molecular drivers of pathological myopia complications vs simple myopia

Year: 2026

Type: article

Abstract: Background Pathological myopia complications are leading causes of irreversible blindness, yet the molecular mechanisms distinguishing them from simple myopia remain poorly understood.We aimed to compare the molecular profiles associated with pathological myopia complications and simple myopia using a multi-omics Mendelian randomisation (MR) framework.Methods Using circulating protein quantitative trait loci data from the INTERVAL study, plasma metabolite genome-wide association study (GWAS) data from the Nightingale Health -UK Biobank initiative and outcome GWAS data for four complication endpoints and myopia from FinnGen R12, together with self-reported myopia from UK Biobank, we performed a two-sample multi-omics MR study.Molecules were classified as complication-specific, myopia-specific, or shared.We performed sensitivity analyses using MR-Egger, weighted median, Steiger directionality, and reverse MR, and assessed classification robustness through threshold-sensitivity and instrument-stratification analyses. ResultsWe identified 872 reliable associations (712 protein and 160 metabolite pairs).Complication-specific proteins (n = 387) outnumbered shared ones (n = 55) by seven to one; similarly, 51 metabolites were complication-specific vs. 9 shared.Six lipoprotein lipid ratio-myopia associations survived false discovery rate (FDR) correction (FDR<0.05),all exclusive to simple myopia.Complication-specific proteins were enriched in axon guidance (adjusted P = 2.0 × 10 -6 ), proteoglycan biosynthesis, and cytokine-cytokine receptor interaction pathways.No robust reverse causation was detected.Top complication-specific targets included endothelin-converting enzyme 1 (odds ratio (OR) = 0.796; P = 4.87 × 10 -5 ) for retinal detachment with break, vascular endothelial growth factor receptor 2 (OR = 1.441;P = 4.94 × 10 -4 ) for retinoschisis, and secreted frizzled-related protein 2 (OR = 1.347;P = 1.41 × 10 -4 ).Conclusions Our analysis indicates that molecular drivers of pathological myopia complications are largely distinct from those of simple myopia, with complication-specific targets enriched in neuronal guidance, extracellular matrix metabolism, and inflammatory signalling.These findings may inform therapeutic strategies aimed at preventing the sight-threatening consequences of myopia.

Source: Journal of Global Health

DOI: 10.7189/jogh.16.04259

Authors: Tong Wang, Aoxiang Wang, Zhongping Chen, Xiaofeng Lin

Institutions: Aier Eye Hospital Group (China), Central South University, Hunan Children's Hospital

Language: English

Topic: Ophthalmology and Visual Impairment Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,200