GWAS on retinal vasculometry phenotypes

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...

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Vydáno v:	PLoS genetics Ročník 19; číslo 2; s. e1010583
Hlavní autoři:	Jiang, Xiaofan, Hysi, Pirro G., Khawaja, Anthony P., Mahroo, Omar A., Xu, Zihe, Hammond, Christopher J., Foster, Paul J., Welikala, Roshan A., Barman, Sarah A., Whincup, Peter H., Rudnicka, Alicja R., Owen, Christopher G., Strachan, David P.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 09.02.2023 Public Library of Science (PLoS)
Témata:	Automation Biobanks Biology and Life Sciences Blood pressure Blood-vessels Cameras Cellular signal transduction Cohort analysis Consortia Genetic aspects Genome-wide association studies Genome-Wide Association Study Genomes Genomics Haplotypes Health services Homeostasis Informed consent Medicine and Health Sciences Metabolism Morphology Phenotype Phenotypes Physiological aspects Questionnaires Research ethics Retina Retinal Vessels Risk Factors Veins & arteries United Kingdom United Kingdom > UK Japan
ISSN:	1553-7404, 1553-7390, 1553-7404
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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.
AbstractList	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 = 2.00x10.sup.-108 ), 2 loci with arteriolar width (rs12969347, p = 3.30x10.sup.-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. 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. 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. 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. 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. 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.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.
Audience	Academic
Author	Owen, Christopher G. Welikala, Roshan A. Foster, Paul J. Barman, Sarah A. Hysi, Pirro G. Mahroo, Omar A. Rudnicka, Alicja R. Hammond, Christopher J. Jiang, Xiaofan Khawaja, Anthony P. Strachan, David P. Xu, Zihe Whincup, Peter H.
AuthorAffiliation	1 UCL Institute of Ophthalmology, London, United Kingdom 4 Section of Ophthalmology, School of Life Course Sciences, King’s College London, London, United Kingdom 8 Population Health Research Institute, St George’s, University of London, London, United Kingdom Case Western Reserve University, UNITED STATES 6 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway 7 Faculty of Science, Engineering and Computing, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey, United Kingdom 2 UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom 3 Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom 5 NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom
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BackLink	https://www.ncbi.nlm.nih.gov/pubmed/36757925$$D View this record in MEDLINE/PubMed
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CitedBy_id	crossref_primary_10_1007_s13167_025_00411_w crossref_primary_10_1038_s41467_024_55198_7 crossref_primary_10_1038_s41467_024_52334_1
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Copyright	Copyright: © 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. COPYRIGHT 2023 Public Library of Science 2023 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2023 Jiang et al 2023 Jiang et al
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