Phenotypic consequences of the GJD2 risk genotype in myopia development

Annechien E.G. Haarman, Clair A. Enthoven, Milly S. Tedja, Jan R. Polling, Willem J.L. Tideman, Jan E.E. Keunen, Camiel J.F. Boon, Janine F. Felix, H. Raat, Annette J.M. Geerards, Gregorius P.M. Luyten, Gwyneth A. van Rijn, Virginie J.M. Verhoeven, Caroline C.W. Klaver*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

PURPOSE. To study the relatively high effect of the refractive error gene GJD2 in human myopia, and to assess its relationship with refractive error, ocular biometry and lifestyle in various age groups. METHODS. The population-based Rotterdam Study (RS), high myopia case-control study MYopia STudy, and the birth-cohort study Generation R were included in this study. Spherical equivalent (SER), axial length (AL), axial length/corneal radius (AL/CR), vitreous depth (VD), and anterior chamber depth (ACD) were measured using standard ophthalmologic procedures. Biometric measurements were compared between GJD2 (rs524952) genotype groups; education and environmental risk score (ERS) were calculated to estimate gene-environment interaction effects, using the Synergy index (SI). RESULTS. RS adults carrying two risk alleles had a lower SER and longer AL, ACD and VD (AA versus TT, 0.23D vs. 0.70D; 23.79 mm vs. 23.52 mm; 2.72 mm vs. 2.65 mm; 16.12 mm vs. 15.87 mm; all P < 0.001). Children carrying two risk alleles had larger AL/CR at ages 6 and 9 years (2.88 vs. 2.87 and 3.00 vs. 2.96; all P < 0.001). Education and ERS both negatively influenced myopia and the biometric outcomes, but gene-environment interactions did not reach statistical significance (SI 1.25 [95% confidence interval {CI}, 0.85–1.85] and 1.17 [95% CI, 0.55–2.50] in adults and children). CONCLUSIONS. The elongation of the eye caused by the GJD2 risk genotype follows a dose-response pattern already visible at the age of 6 years. These early effects are an example of how a common myopia gene may drive myopia.

Original languageEnglish
JournalInvestigative Ophthalmology and Visual Science
Volume62
Issue number10
DOIs
Publication statusPublished - 1 Aug 2021

Bibliographical note

Funding Information:
Supported by the following foundations: Oogfonds, ODAS, Uitzicht 2017-28 (LSBS, MaculaFonds, Oogfonds), Netherlands Organization for Scientific Research (NWO); Grant 91617076 (VJMV) and Grant 91815655 (CCWK), and European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme Grant 648268 (CCWK).

Publisher Copyright:
Copyright 2021 The Authors

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