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Ocular Determinants of Refractive Error and Its Age- and Sex-Related Variations in the Chinese American Eye Study.

ABSTRACT: Importance:Uncorrected refractive error (RE) is a leading cause of visual impairment, and variations in ocular anatomy determine RE. The unique ocular determinants of RE in Chinese American individuals have not been studied previously. Objective:To report ocular determinants of RE in a Chinese American population 50 years and older in Monterey Park, California. Design, Setting, and Participants:The Chinese American Eye Study, a population-based, cross-sectional study, was conducted from February 1, 2010, through October 31, 2013, in Monterey Park, with this particular data analysis performed from January 1 through December 31, 2016. This study included data from 4582 participants who underwent an eye examination to obtain axial length (AL), central corneal thickness, vitreous chamber depth (VCD), anterior chamber depth (ACD), lens thickness (LT), corneal power (CP), noncycloplegic subjective refraction, and lens nuclear opalescence (NOP) grading. Data from the right phakic eye of each participant were used. Multiple regression models (standardized regression coefficients [SRCs] and semipartial correlation coefficients squared [SPCCs2]) identified key determinants of RE. Main Outcomes and Measures:Ocular determinants of RE. Results:Among the 4071 participants eligible for analysis (1496 men [36.7%] and 2575 women [63.3%]; mean [SD] age, 60.5 [8.1] years), mean (SD) RE was -0.52 (2.95) diopters (D), with no sex-related difference. A hyperopic shift occurred in women from -0.62 (2.95) D at 50 to 59 years to 0.60 (1.62) D at 80 years or older and in men from -0.69 (3.00) D at 50 to 59 years to 0.40 (2.29) D at 80 years or older (P < .001 for both). Compared with men, women had shorter AL (mean [SD], 23.62 [1.34] vs 24.14 [1.27] mm; P = .006), shorter ACD (mean [SD], 3.33 [0.34] vs 3.44 [0.34] mm; P < .001), and steeper CP (mean [SD], 43.50 [1.52] vs 42.88 [1.45] D; P = .02), after adjusting for age and height. No sex differences were found in VCD, LT, and NOP after height adjustment. Compared with younger individuals, older individuals had shallower ACD, thicker LT, and more NOP compared with younger individuals (P < .001 for both), even after adjustment for height. Axial length was the strongest determinant of RE (SRC = -0.92; SPCC2 = 0.55), followed by CP (SRC = -0.43; SPCC2 = 0.15). When individual components of AL were evaluated, VCD had the greatest contributing effect (SRC = -0.99; SPCC2 = 0.52), followed by CP (SRC = -0.47; SPCC2 = 0.15) and LT (SRC = -0.29; SPCC2 = 0.06). Conclusions and Relevance:These data suggest that Chinese American individuals have longer AL and greater contribution of AL to RE than do Latino and other Chinese populations. Future studies should explore risk factors for increased AL in Chinese Americans and potential interventions that may ultimately prevent myopia-related disease.

SUBMITTER: Richter GM

PROVIDER: S-EPMC5710201 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeWe sought to investigate anatomic mechanisms of angle narrowing by assessing ocular biometric determinants of anterior chamber angle width.DesignPopulation-based cross-sectional study.MethodsSubjects ≥50 years of age from the Chinese American Eye Study underwent a comprehensive ocular examination, including anterior segment optical coherence tomography imaging and ultrasound A-scan. Independent variables, including anterior chamber depth (ACD), lens vault (LV), iris curvature (IC), anterior chamber width, lens thickness, vitreous cavity depth, and axial length, and dependent variables, including angle opening distance, were measured in 1 randomly selected eye per subject. Univariable and multivariable regression models with standardized regression coefficients (SRCs) and semipartial correlation coefficients squares (SPCC2) were used to assess relative and unique contributions by independent variables to angle width.ResultsTwo thousand two hundred twenty-five subjects (1433 women and 834 men) were included in the analysis. All biometric parameters except lens thickness differed between men and women (age-adjusted P < .001). In model 1A (R2 = 0.66), which included ACD, lens thickness, and vitreous cavity depth, ACD (SRC = 0.64, SPCC2 = 0.19) and IC (SRC = -0.26, SPCC2 = 0.041) were the strongest determinants of angle opening distance. In model 1B (R2 = 0.58), which included LV and axial length, LV (SRC = -0.46, SPCC2 = 0.1) and IC (SRC = -0.3, SPCC2 = 0.047) were the strongest determinants of angle opening distance. Determinants of angle width were similar in separate multivariable models for men and women.ConclusionsACD, LV, and IC are the strongest determinants of angle width in Chinese Americans. Sex-related differences in angle width are explained by differences among biometric measurements. These results provide insights into anatomic mechanisms of angle narrowing and have important implications for quantitative assessments of angle closure eyes.

Project description:Refractive error is a complex trait with multiple genetic and environmental risk factors, and is the most common cause of preventable blindness worldwide. The common nature of the trait suggests the presence of many genetic factors that individually may have modest effects. To achieve an adequate sample size to detect these common variants, large, international collaborations have formed. These consortia typically use meta-analysis to combine multiple studies from many different populations. This approach is robust to differences between populations; however, it does not compensate for the different haplotypes in each genetic background evidenced by different alleles in linkage disequilibrium with the causative variant. We used the Age-Related Eye Disease Study (AREDS) cohort to replicate published significant associations at two loci on chromosome 15 from two genome-wide association studies (GWASs). The single nucleotide polymorphisms (SNPs) that exhibited association on chromosome 15 in the original studies did not show evidence of association with refractive error in the AREDS cohort. This paper seeks to determine whether the non-replication in this AREDS sample may be due to the limited number of SNPs chosen for replication.We selected all SNPs genotyped on the Illumina Omni2.5v1_B array or custom TaqMan assays or imputed from the GWAS data, in the region surrounding the SNPs from the Consortium for Refractive Error and Myopia study. We analyzed the SNPs for association with refractive error using standard regression methods in PLINK. The effective number of tests was calculated using the Genetic Type I Error Calculator.Although use of the same SNPs used in the Consortium for Refractive Error and Myopia study did not show any evidence of association with refractive error in this AREDS sample, other SNPs within the candidate regions demonstrated an association with refractive error. Significant evidence of association was found using the hyperopia categorical trait, with the most significant SNPs rs1357179 on 15q14 (p=1.69×10?³) and rs7164400 on 15q25 (p=8.39×10??), which passed the replication thresholds.This study adds to the growing body of evidence that attempting to replicate the most significant SNPs found in one population may not be significant in another population due to differences in the linkage disequilibrium structure and/or allele frequency. This suggests that replication studies should include less significant SNPs in an associated region rather than only a few selected SNPs chosen by a significance threshold.

Project description:PurposeA previous study of Old Order Amish families showed an association of ocular refraction with markers proximal to matrix metalloproteinase (MMP) genes MMP1 and MMP10 and intragenic to MMP2. A candidate gene replication study of association between refraction and single nucleotide polymorphisms (SNPs) within these genomic regions was conducted.DesignCandidate gene genetic association study.ParticipantsTwo thousand participants drawn from the Age-Related Eye Disease Study (AREDS) were chosen for genotyping. After quality-control filtering, 1912 individuals were available for analysis.MethodsMicroarray genotyping was performed using the HumanOmni 2.5 bead array (Illumina, Inc., San Diego, CA). Single nucleotide polymorphisms originally typed in the previous Amish association study were extracted for analysis. In addition, haplotype tagging SNPs were genotyped using TaqMan assays. Quantitative trait association analyses of mean spherical equivalent refraction were performed on 30 markers using linear regression models and an additive genetic risk model while adjusting for age, sex, education, and population substructure. Post hoc analyses were performed after stratifying on a dichotomous education variable. Pointwise (P(emp)) and multiple-test study-wise (P(multi)) significance levels were calculated empirically through permutation.Main outcome measuresMean spherical equivalent refraction was used as a quantitative measure of ocular refraction.ResultsThe mean age and ocular refraction were 68 years (standard deviation [SD], 4.7 years) and +0.55 diopters (D; SD, 2.14 D), respectively. Pointwise statistical significance was obtained for rs1939008 (P(emp) = 0.0326). No SNP attained statistical significance after correcting for multiple testing. In stratified analyses, multiple SNPs reached pointwise significance in the lower-education group: 2 of these were statistically significant after multiple testing correction. The 2 highest-ranking SNPs in Amish families (rs1939008 and rs9928731) showed pointwise P(emp)<0.01 in the lower-education stratum of AREDS participants.ConclusionsThis study showed suggestive evidence of replication of an association signal for ocular refraction to a marker between MMP1 and MMP10. Evidence of a gene-environment interaction between previously reported markers and education on refractive error also was shown. Variants in MMP1 through MMP10 and MMP2 regions seem to affect population variation in ocular refraction in environmental conditions less favorable for myopia development.

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Ocular Determinants of Refractive Error and Its Age- and Sex-Related Variations in the Chinese American Eye Study.

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