School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom.
Central Research Laboratory, Kazan State Medical University, Kazan, Russia.
Invest Ophthalmol Vis Sci. 2021 Oct 4;62(13):24. doi: 10.1167/iovs.62.13.24.
Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error. We tested the hypothesis that genetic variants regulating eye size in emmetropic eyes are distinct from those conferring susceptibility to refractive error.
A genome-wide association study (GWAS) for corneal curvature in 22,180 adult emmetropic individuals was performed as a proxy for a GWAS for eye size. A polygenic score created using lead GWAS variants was tested for association with corneal curvature and axial length in an independent sample: 437 classified as emmetropic and 637 as ametropic. The genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression for approximately 1 million genetic variants.
The GWAS for corneal curvature in emmetropes identified 32 independent genetic variants (P < 5.0e-08). A polygenic score created using these 32 genetic markers explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of the variance in corneal curvature and axial length, respectively, in the independent sample of emmetropic individuals but was not predictive of these traits in ametropic individuals. The genetic correlation between eye size and refractive error was close to zero (rg = 0.00; SE = 0.06; P = 0.95).
These results support the hypothesis that genetic variants regulating eye size in emmetropic eyes do not overlap with those conferring susceptibility to myopia. This suggests that distinct biological pathways regulate normal eye growth and myopia development.
正视化需要协调主要眼部成分（角膜曲率和眼轴）的比例。这种协调部分是通过一组调节眼睛大小的共同遗传变异来实现的。角膜曲率和眼轴的比例不协调会导致屈光不正。我们检验了以下假设：调节正视眼大小的遗传变异与导致屈光不正易感性的遗传变异不同。
对 22180 名成年正视个体的角膜曲率进行全基因组关联研究（GWAS），作为对眼睛大小的 GWAS 的替代。使用主要 GWAS 变异创建多基因评分，并在独立样本中测试其与角膜曲率和眼轴的相关性：437 名分类为正视，637 名分类为非正视。使用连锁不平衡评分回归计算眼大小和屈光不正之间的遗传相关性，大约使用了 100 万个遗传变异。
正视者的角膜曲率 GWAS 确定了 32 个独立的遗传变异（P < 5.0e-08）。使用这 32 个遗传标记创建的多基因评分分别解释了 3.5%（P < 0.001）和 2.0%（P = 0.001）的角膜曲率和眼轴方差，在独立的正视个体样本中，但不能预测非正视个体的这些特征。眼大小和屈光不正之间的遗传相关性接近零（rg = 0.00；SE = 0.06；P = 0.95）。
这些结果支持了这样的假设，即调节正视眼大小的遗传变异与导致近视易感性的遗传变异不重叠。这表明，不同的生物学途径调节正常眼的生长和近视的发展。
