Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images

Hannah Currant*, Pirro Hysi, Tomas W. Fitzgerald, Puya Gharahkhani, Pieter W.M. Bonnemaijer, Anne Senabouth, Alex W. Hewitt, Denize Atan, Tin Aung, Jason Charng, Hélène Choquet, Jamie Craig, Peng T. Khaw, Caroline C.W. Klaver, Michiaki Kubo, Jue Sheng Ong, Louis R. Pasquale, Charles A. Reisman, Maciej Daniszewski, Joseph E. PowellAlice Pébay, Mark J. Simcoe, Alberta A.H.J. Thiadens, Cornelia M. van Duijn, Seyhan Yazar, Eric Jorgenson, Stuart MacGregor, Chris J. Hammond, David A. Mackey, Janey L. Wiggs, Paul J. Foster, Praveen J. Patel, Ewan Birney, Anthony P. Khawaja

*Corresponding author for this work

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Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

Original languageEnglish
Article numbere1009497
JournalPLoS Genetics
Issue number5
Publication statusPublished - 12 May 2021

Bibliographical note

Funding Information:
H Currant and EB are funded by EMBL. APK was supported by a UK Research & Innovation Future Leaders Fellowship, a Moorfields Eye Charity Career Development Fellowship, and an Alcon Research Institute Young Investigator Award. The Rotterdam Study is funded by Erasmus MC and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. PG is supported by a NHMRC Investigator Grant (#1173390). SM acknowledges Australian National Health and Medical Research Council grants 1154543, 1150144 and 1116360. LRP is funded by NIH EY015473 and also supported by a Challenge Grant from Research to Prevent Blindness, NYC. JW is funded by NIH/NEI P30 EY014104 and R01 EY022305. AH and DM are supported by an Australian National Health and Medical Research Council Practitioner Fellowship. EJ and H Choquet are supported by National Eye Institute (NEI) grant R01 EY027004, by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant R01 DK116738, and by the National Cancer Institute (NCI) grant R01 CA241623. The expression analysis was supported by the Australian National Health and Medical Research Council, the Joan and Peter Clemenger Foundation, and the Ophthalmic Research Institute of Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright: © 2021 Currant 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.


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