Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2021 Oct 26

PMID 34698770

Citations 4

Authors

Denis Plotnikov

Jiangtian Cui

Rosie Clark

Juho Wedenoja

Olavi Parssinen

J Willem L Tideman

Jost B Jonas

Yaxing Wang

Igor Rudan

Terri L Young

David A Mackey

Louise Terry

Cathy Williams

Jeremy A Guggenheim

Affiliations

Soon will be listed here.

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.

Citing Articles

Genetic Correlations Among Corneal Biophysical Parameters and Anthropometric Traits.

Cousins H, Cousins C, Valluru G, Altman R, Liu Y, Pasquale L Transl Vis Sci Technol. 2023; 12(8):8.

PMID: 37561511 PMC: 10424803. DOI: 10.1167/tvst.12.8.8.

A multiethnic genome-wide analysis of 19,420 individuals identifies novel loci associated with axial length and shared genetic influences with refractive error and myopia.

Jiang C, Melles R, Yin J, Fan Q, Guo X, Cheng C Front Genet. 2023; 14:1113058.

PMID: 37351342 PMC: 10282939. DOI: 10.3389/fgene.2023.1113058.

Distribution and Characteristics of Ocular Biometric Parameters among a Chinese Population: A Hospital-Based Study.

Chen X, Huang Y, Chen H, Liu L Ophthalmol Ther. 2023; 12(4):2117-2131.

PMID: 37233976 PMC: 10287596. DOI: 10.1007/s40123-023-00716-x.

A Study Linking Axial Length, Corneal Curvature, and Eye Axis With Demographic Characteristics in the Emmetropic Eyes of Bangladeshi People.

Benzir M, Afroze A, Zahan A, Naznin R, Khanam A, Sumi S Cureus. 2022; 14(10):e29925.

PMID: 36225244 PMC: 9536359. DOI: 10.7759/cureus.29925.

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