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Genome-wide association analysis of 95 549 individuals identifies novel loci and genes influencing optic disc morphology


Han, X and Qassim, A and An, J and Marshall, H and Zhou, T and Ong, J-S and Hassall, MM and Hysi, PG and Foster, PJ and Khaw, PT and Mackey, DA and Gharahkhani, P and Khawaja, AP and Hewitt, AW and Craig, JE and MacGregor, S, Genome-wide association analysis of 95 549 individuals identifies novel loci and genes influencing optic disc morphology, Human Molecular Genetics, 28, (21) pp. 3680-3690. ISSN 0964-6906 (2019) [Refereed Article]

Copyright Statement

Copyright 2019 The Authors

DOI: doi:10.1093/hmg/ddz193


Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer-Norfolk (N = 6005); in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were significant at P < 0.05, with 19 remaining significant after Bonferroni correction. We identified another 26 novel loci in the meta-analysis of UKBB and IGGC data. Gene-based analyses identified an additional 57 genes. Human ocular tissue gene expression analysis showed that most of the identified genes are enriched in optic nerve head tissue. Some of the identified loci exhibited pleiotropic effects with vertical cup-to-disc ratio, intraocular pressure, glaucoma and myopia. These results can enhance our understanding of the genetics of optic disc morphology and shed light on the genetic findings for other ophthalmic disorders such as glaucoma and other optic nerve diseases.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Mackey, DA (Professor David Mackey)
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:137549
Year Published:2019
Web of Science® Times Cited:11
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-02-19
Last Modified:2022-08-25

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