School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF24 4HQ, UK.
Hum Genet. 2018 Dec;137(11-12):881-896. doi: 10.1007/s00439-018-1942-8. Epub 2018 Oct 10.
Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism.
先前的研究表明，自然发生的遗传变异会导致散光风险增加。本研究的目的是在接受角膜曲率计和自动折射检查的大型欧洲血统队列（英国生物库）中，确定与角膜散光和屈光性散光相关的遗传标记。对欧洲血统个体进行了角膜散光和屈光性散光的全基因组关联研究（分别为 86335 人和 88005 人），将同胞眼的平均角膜散光或屈光性散光分析为定量性状（因变量）。使用 LD 得分回归计算这两个性状之间的遗传相关性。使用 MAGMA 进行基因和基因集检验。基于单个标记的角膜散光关联测试确定了四个全基因组显著位点（P<5×10），位于 ZC3H11B（1q41）、LINC00340（6p22.3）、HERC2/OCA2（15q13.1）和 NPLOC4/TSPAN10（17q25.3）基因附近。这三个位点也与屈光性散光全基因组显著相关：LINC00340、HERC2/OCA2 和 NPLOC4/TSPAN10。角膜散光和屈光性散光之间的遗传相关性为 0.85（标准误差=0.068，P=1.37×10）。在这里，我们进行了迄今为止最大的角膜散光和屈光性散光全基因组关联研究，确定了四个新的角膜散光位点，其中两个也是屈光性散光的新位点。这些位点先前与眼轴长度（ZC3H11B）、近视（NPLOC4）、等效球面屈光误差（LINC00340）和眼睛颜色（HERC2）有关。这些新的候选基因在散光中的共同作用进一步支持了近视和散光的共同遗传易感性。
