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Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci

Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent...

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Autores principales: Shah, Rupal L., Guggenheim, Jeremy A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267700/
https://www.ncbi.nlm.nih.gov/pubmed/30306274
http://dx.doi.org/10.1007/s00439-018-1942-8
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author Shah, Rupal L.
Guggenheim, Jeremy A.
author_facet Shah, Rupal L.
Guggenheim, Jeremy A.
author_sort Shah, Rupal L.
collection PubMed
description Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10(−8)) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10(−35)). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00439-018-1942-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-62677002018-12-18 Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci Shah, Rupal L. Guggenheim, Jeremy A. Hum Genet Original Investigation Previous studies have suggested that naturally occurring genetic variation contributes to the risk of astigmatism. The purpose of this investigation was to identify genetic markers associated with corneal and refractive astigmatism in a large-scale European ancestry cohort (UK Biobank) who underwent keratometry and autorefraction at an assessment centre. Genome-wide association studies for corneal and refractive astigmatism were performed in individuals of European ancestry (N = 86,335 and 88,005 respectively), with the mean corneal astigmatism or refractive astigmatism in fellow eyes analysed as a quantitative trait (dependent variable). Genetic correlation between the two traits was calculated using LD Score regression. Gene-based and gene-set tests were carried out using MAGMA. Single marker-based association tests for corneal astigmatism identified four genome-wide significant loci (P < 5 × 10(−8)) near the genes ZC3H11B (1q41), LINC00340 (6p22.3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3). Three of these loci also demonstrated genome-wide significant association with refractive astigmatism: LINC00340, HERC2/OCA2 and NPLOC4/TSPAN10. The genetic correlation between corneal and refractive astigmatism was 0.85 (standard error = 0.068, P = 1.37 × 10(−35)). Here, we have undertaken the largest genome-wide association studies for corneal and refractive astigmatism to date and identified four novel loci for corneal astigmatism, two of which were also novel loci for refractive astigmatism. These loci have previously demonstrated association with axial length (ZC3H11B), myopia (NPLOC4), spherical equivalent refractive error (LINC00340) and eye colour (HERC2). The shared role of these novel candidate genes for astigmatism lends further support to the shared genetic susceptibility of myopia and astigmatism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00439-018-1942-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-10-10 2018 /pmc/articles/PMC6267700/ /pubmed/30306274 http://dx.doi.org/10.1007/s00439-018-1942-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Investigation
Shah, Rupal L.
Guggenheim, Jeremy A.
Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title_full Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title_fullStr Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title_full_unstemmed Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title_short Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci
title_sort genome-wide association studies for corneal and refractive astigmatism in uk biobank demonstrate a shared role for myopia susceptibility loci
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267700/
https://www.ncbi.nlm.nih.gov/pubmed/30306274
http://dx.doi.org/10.1007/s00439-018-1942-8
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