New polygenic risk score predicts high myopia risk in Asian kids

Singapore researchers have developed a novel polygenic risk score (PRS) patterned specifically after Chinese children, improving its predictive performance for future high myopia (HM) in this population.

“We found that adding the PRS to other clinical information, such as child’s age, time outdoors, and parental myopia, improves the prediction of HM risk in teenagers,” the researchers said. “Our findings suggest the potential clinical value of utilizing information on this new Asian PRS together with parental myopia to improve the predictive performance to detect children at risk of HM.”

Drawing from the Singapore Cohort of Risk Factors for Myopia (SCORM), a total of 1,004 children aged 6–11 years were enrolled and followed until their adolescence, at ages 12–18 years. PRS was generated from a large Asian genome-wide association study and a population-wide survey on Chinese families. The developed score was validated in the Growing Up in Singapore Towards Healthy Outcomes cohort.

At the teenage visit, 571 participants remained enrolled in the study, of whom 22.8 percent had moderate myopia (MM) and 23.3 percent had HM. The PRS was calculated for each participant based on 655 single-nucleotide polymorphisms. [Transl Vis Sci Technol 2021;10:26]

The basic model without the PRS included age, sex, maternal education, school, and 10 genotyping principal components. This model could explain 4.0 percent and 10.8 percent of the variance in spherical equivalents (SE) and axial length (AL), respectively.

Adding PRS to the basic model led to a small but significant R² increment of 0.041 (95 percent confidence interval [CI], 0.01–0.073; analysis of variance [ANOVA] p<0.001) for SE and 0.022 (95 percent CI, –0.001 to 0.046; ANOVA p<0.001) for AL. Further inclusion of parental myopia and time outdoors likewise yielded significant improvements to the basic model but had lower magnitudes than that of PRS.

The full multivariable model—including age, time outdoors, parental myopia, and the PRS—could explain 11.9 percent and 15.7 percent of the variance for SE and AL, respectively. Near work, as indicated by the number of books read per week, was not significant.

Area under the curve (AUC) analysis confirmed the value of PRS for predicting HM. A model without PRS had an AUC of 0.72 (95 percent CI, 0.65–0.78) for HM and 0.60 (95 percent CI, 0.53–0.67) for MM. Adding PRS to the model significantly improved its performance for HM (AUC, 0.77, 95 percent CI, 0.71–0.83; p=0.02), but not for MM (AUC, 0.62, 95 percent CI, 0.55–0.69; p=0.36).

Validation of the multivariable model in the GUSTO cohort confirmed its replicability in different cohorts of Chinese ancestry and further underlined the additional predictive value brought about by including PRS into prediction models for HM.

“Clinicians may use the PRS with other predictive factors to identify high risk children and guide interventions to reduce the risk of HM later in life,” the researchers said.

“Further predictive studies with genetic loci from GWAS studies of myopia in East Asians, larger sample sizes, and detailed analyses of ocular and lifestyle factors may be important to increase the predictive performance to a level acceptable for use in clinical application,” they added.