Genetic variants associated with human eye size are distinct from those conferring susceptibility to myopia

Plotnikov, Denis, Cui, Jiangtian, Clark, Rosie, Wedenoja, Juho, Pärssinen, Olavi, Tideman, J. Willem L., Jonas, Jost B., Wang, Yaxing, Rudan, Igor, Young, Terri L., Mackey, David A., Terry, Louise ORCID: https://orcid.org/0000-0002-6200-8230, Williams, Cathy and Guggenheim, Jeremy A. ORCID: https://orcid.org/0000-0001-5164-340X 2021. Genetic variants associated with human eye size are distinct from those conferring susceptibility to myopia. Investigative Ophthalmology & Visual Science 62 (13) , 24. 10.1167/iovs.62.13.24

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Abstract

Purpose: Emmetropization requires coordinated scaling of the major ocular components, corneal curvature and axial length. This coordination is achieved in part through a shared set of genetic variants that regulate eye size. Poorly coordinated scaling of corneal curvature and axial length results in refractive error. We tested the hypothesis that genetic variants regulating eye size in emmetropic eyes are distinct from those conferring susceptibility to refractive error. Methods: A genome-wide association study (GWAS) for corneal curvature in 22,180 adult emmetropic individuals was performed as a proxy for a GWAS for eye size. A polygenic score created using lead GWAS variants was tested for association with corneal curvature and axial length in an independent sample: 437 classified as emmetropic and 637 as ametropic. The genetic correlation between eye size and refractive error was calculated using linkage disequilibrium score regression for approximately 1 million genetic variants. Results: The GWAS for corneal curvature in emmetropes identified 32 independent genetic variants (P < 5.0e-08). A polygenic score created using these 32 genetic markers explained 3.5% (P < 0.001) and 2.0% (P = 0.001) of the variance in corneal curvature and axial length, respectively, in the independent sample of emmetropic individuals but was not predictive of these traits in ametropic individuals. The genetic correlation between eye size and refractive error was close to zero (rg = 0.00; SE = 0.06; P = 0.95). Conclusions: These results support the hypothesis that genetic variants regulating eye size in emmetropic eyes do not overlap with those conferring susceptibility to myopia. This suggests that distinct biological pathways regulate normal eye growth and myopia development.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Advanced Research Computing @ Cardiff (ARCCA) Optometry and Vision Sciences
Additional Information:	This work is licensed under a Creative Commons Attribution 4.0 International License
Publisher:	Association for Research in Vision and Ophthalmology
ISSN:	1552-5783
Funders:	Cardiff University
Date of First Compliant Deposit:	27 October 2021
Date of Acceptance:	4 October 2021
Last Modified:	16 Jul 2024 09:39
URI:	https://orca.cardiff.ac.uk/id/eprint/145095

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