GWAS on retinal vasculometry phenotypes

Abstract

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. Author summary 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.