Proteome-wide Mendelian randomisation identifies causal links between blood proteins and myopia.

ABSTRACT:

Background

Myopia is one of the most prevalent eye diseases worldwide, and its incidence is increasing. However, effective pharmaceutical treatments remain limited. We aimed to identify blood proteins causally associated with myopia as potential drug targets.

Methods

We performed a genome-wide association study (GWAS) meta-analysis involving 43 862 myopia cases and 84 820 controls. Then, we conducted a Mendelian randomisation (MR) analysis of blood proteins by utilising the deCODE and UK Biobank Pharma Proteomics Project datasets, and validated the correlations between these characteristics through a cross-sectional study of 50 586 individuals, including 3108 with myopia. Subsequently, through protein-protein interaction (PPI) analyses, we explored potential connections between proteins and existing myopia treatments.

Results

The GWAS meta-analysis found 26 genetic risk loci for myopia, including nine novel loci. The cross-sectional study showed correlations between height, smoking, and myopia. Proteome-wide MR analysis identified 164 plasma proteins potentially causally linked to myopia, with 20 proteins validated in both datasets. Genetic colocalisation analysis, PPI, and drug target analyses identified promising therapeutic targets for myopia.

Conclusions

We identified genetic loci associated with myopia and proteins with potential causal roles in its development. These results indicate new genetic architectures underlying myopia, offering potential treatment targets and a foundation for personalised therapeutic strategies.

SUBMITTER: Wu F 

PROVIDER: S-EPMC12922467 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature