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A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear

Patasova, Karina; Khawaja, Anthony P; Wojciechowski, Robert; Mahroo, Omar A; Falchi, Mario; Rahi, Jugnoo S; Hammond, Chris J; ... UK Biobank Eye & Vision Consortium; + view all (2022) A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear. Human Molecular Genetics 10.1093/hmg/ddac048. (In press). Green open access

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Abstract

Refractive errors, particularly myopia, are the most common eye conditions, often leading to serious visual impairment. The age of onset is correlated with the severity of refractive error in adulthood observed in epidemiological and genetic studies and can be used as a proxy in refractive error genetic studies. To further elucidate genetic factors that influence refractive error, we analysed self-reported age of refractive error correction data from the UK Biobank European and perform genome-wide time-to-event analyses on the age of first spectacle wear. Genome-wide proportional hazards-ratios analyses were conducted in 340 318 European subjects. We subsequently assessed the similarities and differences in the genetic architectures of refractive error correction from different causes. All-cause age of first spectacle wear (AFSW) was genetically strongly correlated (rg = -0.68) with spherical equivalent (the measured strength of spectacle lens required to correct the refractive error) and was used as a proxy for refractive error. Time-to-event analyses found genome-wide significant associations at 44 independent genomic loci, many of which (GJD2, LAMA2, etc.) were previously associated with refractive error. We also identified six novel regions associated with AFSW, the most significant of which was on chromosome 17q (p = 3.06 x 10-09 for rs55882072), replicating in an independent dataset. We found that genes associated with AFSW were significantly enriched for expression in central nervous system tissues, were involved in neurogenesis. This work demonstrates the merits of time-to-event study design in the genetic investigation of refractive error and contributes additional knowledge on its genetic risk factors in the general population.

Type: Article
Title: A genome-wide analysis of 340 318 participants identifies four novel loci associated with the age of first spectacle wear
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/hmg/ddac048
Publisher version: https://doi.org/10.1093/hmg/ddac048
Language: English
Additional information: © The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
Keywords: UK Biobank Eye & Vision Consortium
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10144756
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