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
Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci.Methods: Here, we conducted a multiethnic genome-wide association st...
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Frontiers Media S.A.
2023-06-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113058/full |
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| author | Chen Jiang Ronald B. Melles Jie Yin Qiao Fan Qiao Fan Xiaobo Guo Xiaobo Guo Ching-Yu Cheng Mingguang He Mingguang He David A. Mackey Jeremy A. Guggenheim Caroline Klaver Consortium for Refractive Error and Myopia (CREAM) K. Saidas Nair Eric Jorgenson Hélène Choquet |
| author_facet | Chen Jiang Ronald B. Melles Jie Yin Qiao Fan Qiao Fan Xiaobo Guo Xiaobo Guo Ching-Yu Cheng Mingguang He Mingguang He David A. Mackey Jeremy A. Guggenheim Caroline Klaver Consortium for Refractive Error and Myopia (CREAM) K. Saidas Nair Eric Jorgenson Hélène Choquet |
| author_sort | Chen Jiang |
| collection | DOAJ |
| description | Introduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci.Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample.Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = −0.83; SE, 0.04; p = 1.95 × 10−89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10−55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04).Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk. |
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| spelling | doaj.art-0e3d0f64229c4614a9eb915fa2c882572023-06-07T05:27:26ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-06-011410.3389/fgene.2023.11130581113058A multiethnic genome-wide analysis of 19,420 individuals identifies novel loci associated with axial length and shared genetic influences with refractive error and myopiaChen Jiang0Ronald B. Melles1Jie Yin2Qiao Fan3Qiao Fan4Xiaobo Guo5Xiaobo Guo6Ching-Yu Cheng7Mingguang He8Mingguang He9David A. Mackey10Jeremy A. Guggenheim11Caroline Klaver12Consortium for Refractive Error and Myopia (CREAM)K. Saidas Nair13Eric Jorgenson14Hélène Choquet15Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, United StatesKPNC, Department of Ophthalmology, Redwood City, CA, United StatesDivision of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, United StatesCentre for Quantitative Medicine, Duke-NUS Medical School, Singapore, SingaporeOphthalmology and Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, SingaporeDepartment of Statistical Science, School of Mathematics, Sun Yat-Sen University, Guangzhou, ChinaSouthern China Center for Statistical Science, Sun Yat-Sen University, Guangzhou, ChinaOcular Epidemiology Research Group, Singapore Eye Research Institute, Singapore, SingaporeState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, ChinaCentre for Eye Research Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, WA, Australia0Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, WA, Australia1School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom2Department Ophthalmology, Department Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands3Department of Ophthalmology and Department of Anatomy, School of Medicine, University of California, San Francisco, CA, United States4Regeneron Genetics Center, Tarrytown, NY, United StatesDivision of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, United StatesIntroduction: Long axial length (AL) is a risk factor for myopia. Although family studies indicate that AL has an important genetic component with heritability estimates up to 0.94, there have been few reports of AL-associated loci.Methods: Here, we conducted a multiethnic genome-wide association study (GWAS) of AL in 19,420 adults of European, Latino, Asian, and African ancestry from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, with replication in a subset of the Consortium for Refractive Error and Myopia (CREAM) cohorts of European or Asian ancestry. We further examined the effect of the identified loci on the mean spherical equivalent (MSE) within the GERA cohort. We also performed genome-wide genetic correlation analyses to quantify the genetic overlap between AL and MSE or myopia risk in the GERA European ancestry sample.Results: Our multiethnic GWA analysis of AL identified a total of 16 genomic loci, of which 5 are novel. We found that all AL-associated loci were significantly associated with MSE after Bonferroni correction. We also found that AL was genetically correlated with MSE (rg = −0.83; SE, 0.04; p = 1.95 × 10−89) and myopia (rg = 0.80; SE, 0.05; p = 2.84 × 10−55). Finally, we estimated the array heritability for AL in the GERA European ancestry sample using LD score regression, and found an overall heritability estimate of 0.37 (s.e. = 0.04).Discussion: In this large and multiethnic study, we identified novel loci, associated with AL at a genome-wide significance level, increasing substantially our understanding of the etiology of AL variation. Our results also demonstrate an association between AL-associated loci and MSE and a shared genetic basis between AL and myopia risk.https://www.frontiersin.org/articles/10.3389/fgene.2023.1113058/fullGWASgeneticssingle nucleotide polymorphisms (SNPs)axial lengtheye biometryrefractive errors |
| spellingShingle | Chen Jiang Ronald B. Melles Jie Yin Qiao Fan Qiao Fan Xiaobo Guo Xiaobo Guo Ching-Yu Cheng Mingguang He Mingguang He David A. Mackey Jeremy A. Guggenheim Caroline Klaver Consortium for Refractive Error and Myopia (CREAM) K. Saidas Nair Eric Jorgenson Hélène Choquet 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 Frontiers in Genetics GWAS genetics single nucleotide polymorphisms (SNPs) axial length eye biometry refractive errors |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | multiethnic genome wide analysis of 19 420 individuals identifies novel loci associated with axial length and shared genetic influences with refractive error and myopia |
| topic | GWAS genetics single nucleotide polymorphisms (SNPs) axial length eye biometry refractive errors |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1113058/full |
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