Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Nat Genet. 2018 Jun;50(6):834-848. doi: 10.1038/s41588-018-0127-7. Epub 2018 May 28.
Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.
屈光不正，包括近视，是全球最常见的眼部疾病，也是失明的一个日益常见的原因。在 160420 名参与者中进行的全基因组关联荟萃分析和在 95505 名参与者中的复制增加了已确定的独立信号数量，从 37 个增加到 161 个，并且显示出欧洲人和亚洲人之间的高度遗传相关性（>0.78）。表达实验和全面的计算分析确定了视网膜细胞生理学和光处理作为主要机制，还确定了在神经感觉视网膜、视网膜色素上皮、血管内皮和细胞外基质的所有细胞类型中对屈光不正发展的功能贡献。新鉴定的基因暗示了新的机制，如视杆和视锥双极突触神经传递、前段形态和血管生成。31 个位点位于转录小 RNA 的区域内或附近，因此表明存在转录后调控的作用。我们的研究结果支持了屈光不正由光依赖性视网膜到巩膜信号级联引起的观点，并描绘了潜在的病理生物学分子驱动因素。
