Polygenic risk score a reliable predictor of high myopia, macular degeneration in Asians

Current polygenic risk scores (PRSs) deliver satisfactory predictive capacity for high myopia (HM) and can pinpoint children at high risk to prevent myopia progression to HM, suggests a Singapore study.

The PRS is also a good predictor for myopic macular degeneration (MMD) and is effective in classifying high-risk adults with myopia who need closer monitoring for myopia-related complications.

In this population-based study, the researchers explored the transancestry portability of current myopic PRSs to predict HM and MMD in an Asian population. They included 5,894 adults (mean age 57.05 years; 2,141 Chinese, 1,913 Indian, and 1,840 Malay) from the Singapore Epidemiology of Eye Diseases study in the current analysis.

Of the participants, 361 were diagnosed with HM (spherical equivalent [SE] <‒5.00 diopters [D]) from refraction measurements, 240 with MMD graded by the International Photographic Classification and Grading System for Myopic Maculopathy criteria from fundus photographs, and 3,774 were control participants without myopic (SE >‒0.5 D). [Ophthalmology 2022;129:890-902]

The researchers derived the PRS from 687,289 HapMap3 single nucleotide polymorphisms (SNPs) from the largest genome-wide association study of myopia in Europeans (n=260,974). They assessed the PRS on its ability to predict patients with HM and MMD compared with controls. The area under the receiver operating characteristic curve (AUROC) to predict HM and MMD was the primary outcome.

The PRS delivered an AUROC of 0.73 (95 percent confidence interval [CI], 0.70‒0.75) for HM and 0.66 (95 percent CI, 0.63‒0.70) for MMD relative to no myopia.

When the PRS was included with other predictors such as age, sex, educational attainment (EA), and ancestry; age-by-ancestry, sex-by-ancestry, and EA-by-ancestry interactions; and 20 genotypic principal components, its AUROC increased to 0.84 (95 percent CI, 0.82‒0.86) for HM and 0.79 (95 percent CI, 0.76‒0.82) for MMD.

Individuals with a PRS in the top 5 percent had 4.66 (95 percent CI, 3.34‒6.42) times greater risk of developing HM and 3.43 (95 percent CI, 2.27‒5.05) times greater risk of developing MMD compared with the remaining 95 percent.

“The PRS is a good predictor for HM and facilitates the identification of high-risk children to prevent myopia progression to HM,” the researchers said. “In addition, the PRS also predicts MMD and helps to identify high-risk adults with myopia who require closer monitoring for myopia-related complications.”

In an earlier study, close to 1 billion people are projected to develop HM by 2050, 7.5 times more than in 2000. This projection integrated local, individual studies into an improved global understanding of myopia epidemiologic factors. [Ophthalmology 2016;123:1036-1042]

“If correct, our projections have significant implications for planning comprehensive eye care services globally,” the authors said. “The benefits of a multifaceted myopia control system to buffer this scenario would be substantial.”

Myopia is a common cause of vision loss, and uncorrected myopia is the leading cause of distance vision impairment across the globe. [Ophthalmology 2016;123:1036-1042]