机构：[1]School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom[2]Central Research Laboratory, Kazan State Medical University, Kazan, Russia[3]Department of Ophthalmology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland[4]Department of Public Health, University of Helsinki, Helsinki, Finland[5]Gerontology Research Center and Faculty of Sport and Health Sciences, University of Jyvaskyla Jyvaskyla Finland[6]Department of Ophthalmology, Erasmus Medical Centre, Rotterdam, The Netherlands[7]Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands[8]Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany[9]Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[10]Institute of Molecular and Clinical Ophthalmology, Basel, Switzerland[11]Centre for Global Health and WHO Collaborating Centre, University of Edinburgh, United Kingdom[12]Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison, Madison, Wisconsin, United States[13]Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Australia[14]Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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 (r(g) = 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.
基金：
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.
第一作者机构：[1]School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom[2]Central Research Laboratory, Kazan State Medical University, Kazan, Russia
通讯作者：
通讯机构：[1]School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom[*1]School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK
推荐引用方式(GB/T 7714)：
Plotnikov Denis,Cui Jiangtian,Clark Rosie,et al.Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia[J].INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE.2021,62(13):doi:10.1167/iovs.62.13.24.
APA：
Plotnikov, Denis,Cui, Jiangtian,Clark, Rosie,Wedenoja, Juho,Parssinen, Olavi...&Guggenheim, Jeremy A..(2021).Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,62,(13)
MLA：
Plotnikov, Denis,et al."Genetic Variants Associated With Human Eye Size Are Distinct From Those Conferring Susceptibility to Myopia".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 62..13(2021)
