Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
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DOI：
10.1038/s42003-020-0802-y
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发表时间：
2020-03-19
影响因子：
5.9
通讯作者：
Cheng, Ching-Yu
中科院分区：
文献类型：
--
作者：
Fan, Qiao;Pozarickij, Alfred;Cheng, Ching-Yu
角膜曲率是一种高度可遗传的性状，是近视的关键临床表型。近视是世界上视力损害和失明的主要原因。在这里，我们提出了一项跨种族的角膜曲率的荟萃分析，在44,042名高加索人和亚洲人中进行，重复在88,218英国生物库数据中。我们确定了47个基因座(其中26个是新的)，具有特定于人群的信号以及跨种族共享的信号。一些已识别的变体显示了角膜曲率和眼睛伸长(即眼轴长度)的精确比例，以维持正视状态下的眼睛(即HDAC11/FBLN2rs2630445，RBP3rs11204213)；另一些变体显示与近视有关，对眼睛伸长几乎没有多效性影响。涉及的基因涉及细胞外基质组织、身体和眼睛的发育过程、结缔组织软骨和糖基化蛋白活性。我们的研究提供了对人群特有的角膜曲率新基因的洞察，以及它们在调节眼睛大小或增加近视易感性方面的多效性作用。报道了一项对超过4.5万名欧洲或亚洲血统的人进行的全基因组角膜曲率关联分析。角膜曲率是识别视力问题(如近视)的重要指标。他们确定了47个基因座，其中26个是新的，其中一些显示了人群特有的效应和对眼睛延长和近视的多效性效应。
Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.Qiao Fan et al. report a genome-wide association analysis of corneal curvature-an important measurement for identifying vision problems, such as myopia-in more than 45,000 individuals of either European or Asian ancestry. They identify 47 loci, 26 of which are novel, with some showing population-specific effects and pleiotropic effects on eye elongation and myopia.