Gene polymorphisms associated with corneal curvature, astigmatism and its vector components in children

While parental astigmatism is a known risk factor for childhood astigmatism, the molecular genetic basis remains elusive. Previous genetic studies, largely confined to adult corneal and refractive astigmatism (CA and RA), did not address internal astigmatism (IA) and astigmatism vector components. We aimed to determine whether genes previously identified to have associations with corneal curvature (CR), CA, and RA in adults similarly occur for CR, CA, RA, IA, and astigmatism vector components (J0 and J45) in children.

Fourteen polymorphisms in nine loci were genotyped in 2167 Chinese children. Linear and logistic regression analyses were conducted to evaluate the association of the polymorphisms with CR, CA, RA, IA, and astigmatism vector components, which were determined by keratometry, cycloplegic refraction, or Fourier transformation.

FMNL2 rs1579050 was associated with CA (additive: β = 0.158, P = 0.0028; dominant: β = 0.163, P = 0.0034), J0_(CA) (additive: β = 0.081, P = 0.0031), and an increased risk of dichotomous RA (additive: OR = 1.609, P = 0.0028; dominant: OR = 1.671, P = 0.0020), whereas NHSL1 rs4896367 was associated with J0_(IA) (recessive: β = 0.058, P = 0.0002) and a lower risk of dichotomous IA (recessive: OR = 0.577, P = 0.0007). PDGFRA rs2228230 was also associated with J0_(IA) (dominant: β = -0.034, P = 0.0012). The predisposition to CA and RA increased with the risk alleles of FMNL2 rs1579050.

These findings reveal genetic contributions to childhood astigmatism and demonstrate that vector-based decomposition may facilitate more precise mapping of its genetic determinants.