Abstract
BackgroundMyopia is a common eye disorder that is approaching epidemic proportions worldwide. A genome-wide association study identified AREG (rs12511037), GABRR1 (rs13215566), and PDE10A (rs12206610) as being associated with refractive error in Asian populations. The present study investigated the associations between these three genetic variants and the occurrence and development of myopia, spherical equivalent refraction (SER), axial length (AL), and corneal curvature (CC) in a cohort of southeastern Chinese schoolchildren.MethodsWe examined and followed 550 children in grade 1 enrolled in the Wenzhou Epidemiology of Refractive Error (WERE) project. During the 4-year follow-up, non-cycloplegic refraction was evaluated twice each year, and the AL and CC were measured once every year. Age, sex, and the amounts of time spent on near work and outdoors were documented with a questionnaire. Sanger DNA sequencing was used to genotype single nucleotide polymorphisms (SNPs). SNPtest software was used to identify potential genetic variants associated with myopia, SER, AL, and CC. Ten thousand permutations were used to correct for multiple testing.ResultsIn total, 469 children, including 249 (53.1%) boys and 220 (46.9%) girls, were included in analyses. The mean age of all the children was 6.33 ± 0.48 years. After adjusting for age, sex, time spent on near work and time spent outdoors, neither the genotypes nor the allele frequencies of the three SNPs were significantly associated with myopic shift, incident myopia or the change in SER. After adjusting for age, sex, near-work time and outdoor time with 10,000 permutations, the genotype AREG (rs12511037) was associated with an increase in AL (P′-values for the dominant, recessive, additive and general models were 0.0032, 0.0275, 0.0045, and 0.0099, respectively); the genotype PDE10A (rs12206610) was associated with a change in CC in the additive (P′ = 0.0096), dominant (P′ = 0.0096), and heterozygous models (P′ = 0.0096).ConclusionThese findings preliminarily indicate that AREG SNP rs12511037 and PDE10A SNP rs12206610 are etiologically relevant for ocular traits, providing a basis for further exploration of the development of myopia and its molecular mechanism. However, elucidating the role of AREG and PDE10A in the pathogenesis of myopia requires further animal model and human genetic epidemiology studies. This trial is registered as ChiCTR1900020584 at www.Chictr.org.cn.
Highlights
Myopia is a common eye disorder that is reaching epidemic proportions worldwide (Williams et al, 2015; Wang et al, 2018; Tideman et al, 2019)
The few studies performed in the Asian population have determined the potential genetic susceptibility loci for refractive error, including GJD2 (Cheng et al, 2013; Miyake et al, 2015), AKAP13 (Cornes et al, 2012), LAMA2 (Cheng et al, 2013), and WNT7B (Miyake et al, 2015), etc
Incident myopia was defined as the proportion of children who were non-myopic at baseline but who subsequently developed myopia during the follow-up period
Summary
Myopia (nearsightedness) is a common eye disorder that is reaching epidemic proportions worldwide (Williams et al, 2015; Wang et al, 2018; Tideman et al, 2019). The global prevalence of myopia is increasing and expected to increase from one in four persons in 2000 to nearly half of the global population by 2050 (Holden et al, 2016). It is generally characterized by axial elongation of the eye, accompanied by structural changes in the choroid and retina. Fan et al (2016) reported that three novel loci, AREG (rs12511037), GABRR1 (rs13215566), and PDE10A (rs12206610), were associated with refractive error only in the Asian population. A genome-wide association study identified AREG (rs12511037), GABRR1 (rs13215566), and PDE10A (rs12206610) as being associated with refractive error in Asian populations. The present study investigated the associations between these three genetic variants and the occurrence and development of myopia, spherical equivalent refraction (SER), axial length (AL), and corneal curvature (CC) in a cohort of southeastern Chinese schoolchildren
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