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Association analysis of exome variants and refraction, axial length, and corneal curvature in a European-American population.

ABSTRACT: Refractive errors, myopia, and hyperopia are common visual disorders greatly affecting older individuals. Refraction is determined by genetic factors but only a small percentage of its variation has been explained. We performed a genetic association analysis with three ocular phenotypes: spherical equivalent (a continous measure of refraction), axial length, and corneal curvature in 1,871 European-Americans from the Beaver Dam Eye Study. Individuals were genotyped on the Illumina exome array and imputed to the Haplotype Reference Consortium reference panel. After increasing the number of analyzed variants in targeted protein-coding regions 10-fold via imputation, we confirmed associations for two previously known loci with corneal curvature (chr4q12, rs2114039; g.55092626T > C, ? = -0.03 (95% confidence interval [CI]): -0.06, -0.01, P value = 0.01) and spherical equivalent (chr15q14, rs634990; g.35006073T > C, ? = -0.27, 95% CI: -0.45, -0.09, P value = 3.79 × 10-3 ). Despite increased single nucleotide polymorphism (SNP) density, we did not detect any novel significant variants after correction for multiple comparisons. In summary, we confirmed two previous loci associated with corneal curvature and spherical equivalent in a European-American population highlighting the potential biological role of those regions in these traits.

SUBMITTER: Vergara C

PROVIDER: S-EPMC6497529 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association analysis of exome variants and refraction, axial length, and corneal curvature in a European-American population.

Vergara Candelaria C Bomotti Samantha M SM Valencia Cristian C Klein Barbara E K BEK Lee Kristine E KE Klein Ronald R Klein Alison P AP Duggal Priya P

Human mutation 20180911 12

Refractive errors, myopia, and hyperopia are common visual disorders greatly affecting older individuals. Refraction is determined by genetic factors but only a small percentage of its variation has been explained. We performed a genetic association analysis with three ocular phenotypes: spherical equivalent (a continous measure of refraction), axial length, and corneal curvature in 1,871 European-Americans from the Beaver Dam Eye Study. Individuals were genotyped on the Illumina exome array and ...[more]

PMID: 30157304

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Project description: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.

Project description:AimsTo determine the characteristics of corneal biometrics in eyes from aniso-axial length cataract patients compared with eyes from non-aniso-axial length individuals.MethodsThis is a retrospective case series. Cataract patients with preoperative binocular measurements were recruited. A binocular axial difference of ≥1 mm was considered to indicate aniso-axial length. The anterior segmental biometrics were measured using Pentacam HR (Oculus, Wetzlar, Germany) and IOLMaster 500 (Carl Zeiss Meditec, Jena, Germany). Comparisons of biometrics were made among 4 eye conditions: the longer eyes from aniso-axial length patients, the shorter eyes from aniso-axial length patients, the longer eyes from non-aniso-axial length patients, and the shorter eyes from non-aniso-axial length patients. The aniso-axial length eyes were also stratified into 8 subgroups with axial length (AL) increments of 1 mm, and the biometrics of the subgroups were compared.ResultsThere was smaller anterior corneal astigmatism in the shorter aniso-axial length group than those in the longer aniso-axial length group (1.01 ± 0.70 D vs 1.12 ± 0.76 D, P=0.031). The longer aniso-axial length eyes had greater anterior corneal steep curvature (44.13 ± 1.69 D vs 43.87 ± 1.69 D, P=0.009) and anterior corneal astigmatism (1.12 ± 0.76 D vs 1.02 ± 0.69 D, P=0.023) compared with longer non-aniso-axial length subjects. Other corneal biometrics were similar between the aniso-axial length eyes and the non-aniso-axial length eyes. In the longer aniso-axial length group, the posterior corneal aberrations of eyes in the ≥5 mm subgroups were greater than those in the <5 mm subgroups (0.879 ± 0.183 μm vs 0.768 ± 0.178 μm for total aberrations, P < 0.001; 0.228 ± 0.086 μm vs 0.196 ± 0.043 μm for high-order aberrations, P=0.036; 0.847 ± 0.173 μm vs 0.741 ± 0.179 μm for low-order aberrations, P=0.001).ConclusionEyes of aniso-axial length individuals share generally similar corneal biometrics with normal eyes in cataract population. Anterior corneal astigmatism of the longer eyes from the aniso-axial length cataract patients was higher than that of the longer eyes from the non-aniso-axial length individuals. Total posterior corneal aberrations of the longer aniso-axial length eyes increased when the binocular axial difference was over 5 mm.

Dataset Information

Association analysis of exome variants and refraction, axial length, and corneal curvature in a European-American population.

Publications

Association analysis of exome variants and refraction, axial length, and corneal curvature in a European-American population.

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