Identifying potential therapeutic targets for high myopia via a case-control study and Mendelian randomisation analyses of the human blood metabolome

High myopia increases the risk of pathological ocular changes that may lead to irreversible vision loss. Therefore, the identification of potential biomarkers and therapeutic targets for high myopia is essential for early intervention and prevention.

Summary statistics for 122 blood metabolites were obtained from three genome-wide association studies (GWASs), whereas data on high myopia were derived from a large GWAS conducted with 50,372 participants from the UK Biobank. Mendelian randomisation (MR) analyses were conducted to assess the causal relationships between blood metabolites and high myopia. A real-world case-control study was conducted to validate the causal associations identified in the MR analyses.

The systematic MR analysis identified 5 blood metabolites as both biomarkers and potential drug targets for high myopia, including glutamine (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.97–1.00), tyrosine (OR: 0.98; 95% CI: 0.97–0.99), degree of unsaturation (OR: 0.98, 95% CI: 0.98–0.99), docosahexaenoic acid (DHA) (OR: 0.99; 95% CI: 0.98–1.00) and isobutyrylcarnitine (OR: 1.09, 95% CI: 1.05–1.13). The case-control study indicated that the levels of glutamine (OR = 0.76, 95% CI: 0.58–0.98) and tyrosine (OR = 0.72, 95% CI: 0.55–0.94) were significantly associated with a decreased risk of high myopia.

Systematic MR analysis suggested that glutamine, tyrosine, the degree of unsaturation, DHA, and isobutyrylcarnitine may represent promising drug targets for high myopia prevention. Further investigations are needed to validate the therapeutic efficacy and elucidate the underlying mechanisms involved.