Associations of genetic variants for refractive error and axial length in adults with ocular endophenotypes in children: a cross-sectional and longitudinal study.

Abstract

To investigate the associations of genetic variants previously linked to axial length (AL) and spherical equivalent refraction (SE) in adults with refractive error and related endophenotypes in children, at baseline and 3-year follow-up. 15 candidate single-nucleotide polymorphisms (SNPs), selected from previous Genome-Wide Association Studies and meta-analyses, were genotyped in 2819 Chinese children, who had undergone baseline and 3-year follow-up cycloplegic refraction, ocular biometry and ocular health examinations. Linear regression analyses were conducted to assess the associations of the SNPs with baseline measurements and longitudinal changes in SE, spherical power (SPH), AL, corneal radius of curvature (CR) and AL/CR ratio. SNPs <i>ZMAT4</i> rs7829127, <i>ZMAT4</i> rs16890057, <i>TOX</i> rs7837791, <i>GRIA4</i> rs11601239 and <i>RDH5</i> rs3138142 were associated with SE (β=0.233, p=4.21×10^-4; β=0.221, p=7.87×10^-4; β=0.106, p=0.0076; β=0.084, p=0.041; β=0.14, p=0.013, respectively) and SPH (β=0.24, p=2.3×10^-4; β=0.232, p=3.8×10^-4; β=0.088, p=0.025; β=0.086, p=0.034; β=0.14, p=0.012, respectively). Among them, <i>ZMAT4</i> rs7829127 and rs16890057, were also associated with AL (β=-0.128, p=5.6×10^-4; β=-0.128, p=5.21×10^-4) and AL/CR ratio (β=-0.014, p=0.0028; β=-0.014, p=0.0034), whereas <i>TOX</i> rs7837791 was associated with AL (β=-0.062, p=0.0058) and <i>GRIA4</i> 11 601 239 with AL/CR ratio (β=-0.0058, p=0.049). Additionally, <i>CD55</i> rs1652333 and <i>RDH5</i> rs3138142 were associated with 3-year longitudinal changes in AL (β=0.062, p=0.018; β=-0.079, p=0.029) and CR (β=0.014, p=0.027; β=-0.018, p=0.035). Among SNPs previously associated with AL and SE in adults, variants in <i>ZMAT4</i>, <i>TOX</i> and <i>GRIA4</i> were associated with AL, SE, SPH, and/or AL/CR ratio, while variants in <i>RDH5</i> and <i>CD55</i> showed associations with AL and CR changes in children.