Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is often used to diagnose and manage multiple ophthalmic diseases including glaucoma. We present the first large-scale quantitative genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has previously been associated with glaucoma, and Mendelian randomisation confirms that inner retinal thickness, despite being a valid biomarker for the disease, is not on the same genetic causal pathway as glaucoma. Image analysis methods were used to extract overall retinal thickness at the fovea, representative of hypoplasia, with which three out of the 46 SNPs were associated. These SNPs have been previously linked with pigmentation, confirmed by their association with hair colour in the UK Biobank dataset. We additionally associate these three loci with visual acuity. In contrast to the already known Mendelian causes of severe foveal hypoplasia, our results suggest a previously unknown spectrum of foveal hypoplasia in the population, in part genetically determined, that has consequences on visual function.

中文翻译：

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遗传变异影响从UK Biobank光学相干断层扫描图像提取的形态学视网膜表型

光学相干断层扫描（OCT）可以对视网膜进行非侵入性成像，通常用于诊断和处理包括青光眼在内的多种眼科疾病。我们目前使用来自31,434位英国Biobank参与者的OCT图像的表型对视网膜内部形态进行大规模的全基因组关联研究。我们确定与视网膜神经纤维层或神经节细胞内丛状层厚度相关的46个基因座。这些基因座中只有一个以前与青光眼有关，孟德尔随机法证实，尽管视网膜内膜厚度是该病的有效生物标记，但其与青光眼的遗传因果途径不同。图像分析方法用于提取中央凹处视网膜的整体厚度，代表发育不全，与46个SNP中的三个相关联。这些SNP以前与色素沉着有关，在UK Biobank数据集中通过与头发颜色的关联得到证实。我们还将这三个基因座与视敏度相关联。与孟德尔严重的中央凹发育不全的已知原因相反，我们的结果表明，该人群中中央凹发育不全的频谱以前未知，部分是遗传确定的，对视觉功能有影响。