1School of Optometry & Vision Sciences, Cardiff University, Cardiff, CF24 4HQ UK.
2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN UK.
Commun Biol. 2019 May 6;2:167. doi: 10.1038/s42003-019-0387-5. eCollection 2019.
A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance ( < 1.1 × 10) and 128 (88%) at nominal significance ( < 0.05). variant rs12193446, for example, had an effect size varying from -0.20 diopters (95% CI -0.18 to -0.23) to -0.89 diopters (95% CI -0.71 to -1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive.
遗传因素对屈光不正的影响已被全基因组关联研究（GWAS）中发现的 150 多个相关变异所证实。环境因素，如教育和户外活动时间，也与屈光不正有很强的相关性。然而，目前近视的基因-环境或基因-基因相互作用的程度尚不清楚。我们检验了这样一个假设，即与屈光不正相关的变异体表现出效应大小异质性，这是遗传相互作用的一个显著特征。在 146 个测试的变体中，有 66 个（45%）在 Bonferroni 校正显著水平（ < 1.1 × 10）和 128 个（88%）在名义显著水平（ < 0.05）下观察到非均匀、非线性效应的证据。例如，变异体 rs12193446 在不同个体中的效应大小从 -0.20 屈光度（95%CI -0.18 至 -0.23）到 -0.89 屈光度（95%CI -0.71 至 -1.07）不等。SNP 效应在表型极端值最强，在正视眼较弱。这些发现的一个简单解释是，近视中的基因-环境或基因-基因相互作用是普遍存在的。
