As concern mounts over myopia’s worldwide proliferation, researchers are seeking clues about its genesis and associated risk factors in hopes that a better understanding of pathophysiology might point clinicians toward more precise interventions. A recent paper published in JAMA Ophthalmology suggests a single set of common genetic variants may play a role in individuals’ susceptibility to high and low myopia and hyperopia.
Specifically, the multi-international investigative team found genetic risk variants were shared across European and Asian individuals with high and low myopia or hyperopia.
Additionally, high myopes inherited a higher number of variants from the same set of myopia-predisposing alleles as individuals with low myopia, according to the study.
“This work provides further evidence that the genetic contribution to refractive error is primarily polygenic,” the researchers wrote in their paper. “Genetic variants with risk alleles associated with myopia were common in individuals with low myopia, even more common in those with high myopia, but less common in those with hyperopia.”
The genetic association study assessed unrelated UK Biobank participants between the ages of 40 and 69 of European and Asian ancestry (52,000 unrelated individuals of European ancestry and 2,000 unrelated individuals of Asian ancestry).
The researchers divided participants into four refractive error groups: high myopia (-6.00D or less), low myopia (-3.00D to -1.00D), hyperopia (+2.00D or greater) and emmetropia (0.00D to +1.00D). Additionally, four genome-wide association study analyses were performed in participants of European ancestry: high myopia vs. emmetropia, low myopia vs. emmetropia, hyperopia vs. emmetropia and low myopia vs. hyperopia.
Polygenic risk scores derived from all four genome-wide association analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the high myopia vs. emmetropia analyses was predictive of the European sample of high myopia vs. emmetropia, as well as low myopia vs. emmetropia, hyperopia vs. emmetropia and low myopia vs. hyperopia.
These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both low and high myopia, the authors said.
Tideman JWL, Pärssinen O, Haarman AEG, et al. Evaluation of shared genetic susceptibility to high and low myopia and hyperopia. JAMA Ophthalmol. April 8, 2021. [Epub ahead of print].