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.
| Original language | English |
|---|---|
| Article number | 24 |
| Pages (from-to) | 24 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 62 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 4 Oct 2021 |
Bibliographical note
Funding Information:Supported by the Welsh Government and Fight for Sight (24WG201 to JAG and CW), the Global Education program of the Russian Federation government (DP), and an NIHR Senior Research Fellowship award (SRF-2015-08-005 to CW). ALSPAC GWAS data were generated by the Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp using support from 23andMe.The sponsor or funding organizations had no role in the design or conduct of this research.
Funding Information:
Supported by the Welsh Government and Fight for Sight (24WG201 to JAG and CW), the Global Education program of the Russian Federation government (DP), and an NIHR Senior Research Fellowship award (SRF-2015-08-005 to CW). ALSPAC GWAS data were generated by the Sample Logistics and Geno-typing Facilities at Wellcome Sanger Institute and LabCorp using support from 23andMe.The sponsor or funding organizations had no role in the design or conduct of this research.
Funding Information:
This research was conducted using the UK Biobank Resource (application #17351). UK Biobank was established by the Wellcome Trust (London, UK), UK Medical Research Council (Swin-don, UK), Department of Health and Social Care (London, UK), Scottish Government (Edinburgh, UK), and Northwest Regional Development Agency (Warrington, UK). It also received funding from the Welsh Assembly Government (Cardiff, UK), British Heart Foundation (London, UK), and Diabetes UK (London, UK). The collection of eye and vision data was supported by the Department of Health and Social Care through an award made by the National Institute for Health Research to the Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology (London, UK; BRC2_009). Additional support was provided by the Special Trustees of Moorfields Eye Hospital (London, UK; ST 12 09). A grant from the UK Medical Research Council and Wellcome (217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. Data analysis was carried out using the HAWK computing cluster, maintained by Supercomputing Wales and Cardiff University ARCCA.
Publisher Copyright:
Copyright 2021 The Authors.