Multi-Ancestry, Multitrait Polygenic Risk Scores for Myopia: Improved Accuracy and Clinical Potential

Area of Science:

• Ophthalmology
• Genetics
• Public Health

Background:

• Myopia is a growing global health issue and a primary cause of vision impairment.
• Genetic factors significantly contribute to myopia development.
• Current polygenic risk scores (PRSs) often lack accuracy across diverse ancestries due to European-centric data.

Purpose of the Study:

• To develop and assess PRSs for spherical equivalent refractive error (SER) and myopia using multi-ancestry data.
• To evaluate the predictive performance of these PRSs across different ancestral populations.
• To explore the potential of multi-trait, multi-ancestry PRSs for early and equitable myopia risk stratification.

Main Methods:

• Utilized multitrait and multi-ancestry genomewide association study data.
• Generated PRSs using SBayesRC for individual and combined ancestry models.
• Validated PRSs in the Australian Twins Eye Study and UK Biobank participants.

Main Results:

• European PRSs explained up to 20% of SER variance in Europeans and showed transferability to other ancestries.
• A multi-ancestry PRS improved prediction in African populations.
• PRSs accurately predicted high myopia risk (AUC ≥ 0.70) and axial length in children.
• PRSs showed good predictive accuracy across diverse ancestral groups, with a multi-ancestry model enhancing prediction in African populations.

Conclusions:

• Multi-trait, multi-ancestry PRSs significantly enhance the genetic prediction of myopia.
• These advanced PRSs hold potential for early and equitable risk stratification in children.
• Improved genetic prediction can aid in developing targeted interventions for myopia prevention and management.