Abstract
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.
Original language | English |
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Article number | 1113058 |
Journal | Frontiers in Genetics |
Volume | 14 |
DOIs | |
Publication status | Published - 7 Jun 2023 |
Bibliographical note
Funding Information:Genotyping of the GERA cohort was funded by a grant from the National Institute on Aging, National Institute of Mental Health, and National Institute of Health Common Fund (RC2AG036607). Support for GERA participant enrollment, survey completion, and biospecimen collection for the Research Program on Genes, Environment and Health was provided by the Robert Wood Johnson Foundation, the Wayne and Gladys Valley Foundation, the Ellison Medical Foundation, and Kaiser Permanente Community Benefit Programs. The study was funded by the National Eye Institute (NEI) (R01EY027004 to HC). KSN is supported by NEI R01EY032666.
Publisher Copyright:
Copyright © 2023 Jiang, Melles, Yin, Fan, Guo, Cheng, He, Mackey, Guggenheim, Klaver, Nair, Jorgenson and Choquet.