GWAS on retinal vasculometry phenotypes.
GWAS on retinal vasculometry phenotypes.
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DOI：
10.1371/journal.pgen.1010583
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发表时间：
2023-02
期刊：
影响因子：
4.5
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中科院分区：
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眼睛是光传递和视觉感觉信号产生的窗口。它也是一个窗口，通过它可以使用检眼镜或视网膜成像直接检查心血管和神经系统的成分。因此，眼球参数的测量可以提供有关这两个重要系统的生理和动态平衡的重要信息。在这里，我们报告了视网膜血管系统的遗传特征的结果。对视网膜血管测量表型的不同方面进行的四项全基因组关联研究，如小动脉和小静脉的曲度和宽度，发现视网膜血管特征和心脏代谢健康之间有显著的相似之处。我们的分析发现了119个不同的与视网膜血管特性相关的区域，包括89个与微动脉弯曲相关的基因座，其中最强的是rs35131825(p=2.00×10−108)，2个与微动脉宽度相关的基因座(rs12969347，p=3.30×10−09和rs5442，p=1.9E-15)，另外17个与小静脉弯曲相关的基因座和11个新的与静脉宽度相关的基因座。我们的因果推断分析还发现，与小动脉弯曲有关的因素会导致舒张压升高，而不是相反。眼球后部的血管(“视网膜”)很容易被成像。据我们所知，这是迄今为止对视网膜血管形状和大小特征进行的最大规模的遗传学研究。我们的研究在使用自动人工智能成像方法区分动脉和静脉方面是新颖的，并且比以前的任何研究(总共119个遗传位点)证明了更多的基因与血管特征的关联。我们还表明，视网膜动脉的曲折是最强烈的遗传决定的血管特征(在另一个单独的第二个大型数据集中复制得很好)。此外，使用一种特殊类型的基因分析(所谓的孟德尔随机化)，我们首次表明视网膜动脉的曲折与舒张压升高有因果关系，而不是相反。这一点很重要，因为它为高血压和高血压的机制提供了独特的见解，为未来的治疗提供了新的治疗靶点。
The eye is the window through which light is transmitted and visual sensory signalling originates. It is also a window through which elements of the cardiovascular and nervous systems can be directly inspected, using ophthalmoscopy or retinal imaging. Measurements of ocular parameters may therefore offer important information on the physiology and homeostasis of these two important systems. Here we report the results of a genetic characterisation of retinal vasculature. Four genome-wide association studies performed on different aspects of retinal vasculometry phenotypes, such as arteriolar and venular tortuosity and width, found significant similarities between retinal vascular characteristics and cardiometabolic health. Our analyses identified 119 different regions of association with traits of retinal vasculature, including 89 loci associated arteriolar tortuosity, the strongest of which was rs35131825 (p = 2.00×10−108), 2 loci with arteriolar width (rs12969347, p = 3.30×10−09 and rs5442, p = 1.9E-15), 17 other loci associated with venular tortuosity and 11 novel associations with venular width. Our causal inference analyses also found that factors linked to arteriolar tortuosity cause elevated diastolic blood pressure and not vice versa. Vessels at the back of the eye (the “retina”) can be imaged easily. This paper reports on the largest genetic study of retinal vessel shape and size characteristics so far undertaken, to the best of our knowledge. Our study is novel in using an automated artificial intelligence imaging approach to distinguish between arteries and veins, and in demonstrating more genetic associations with vessel characteristics than any previous study (119 genetic loci in all). We also show that the tortuosity of retinal arteries is the most strongly genetically determined vessel characteristic (replicated remarkable well in a separate second large dataset). In addition, using a particular type of genetic analysis (so called “Mendelian Randomization”) we show for the first time that the tortuosity of arteries in the retina is causally related to elevated diastolic blood pressure and not the other way around. This is important as it provides unique insights into the mechanism of elevated blood pressure and hypertension, providing pointers to novel therapeutic targets for future treatment.