An evaluation of OPTC and EPYC as candidate genes for high myopia.
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ABSTRACT:
SUBMITTER: Wang P
PROVIDER: S-EPMC2763122 | biostudies-literature | 2009 Oct
REPOSITORIES: biostudies-literature
Publications
An evaluation of OPTC and EPYC as candidate genes for high myopia.
Wang Panfeng P Li Shiqiang S Xiao Xueshan X Guo Xiangming X Zhang Qingjiong Q
Molecular vision 20091015
<h4>Purpose</h4>The small leucine-rich repeat proteins (SLRPs) are involved in organizing the collagen fibrils of the sclera and vitreous. The shape of the eyeball is determined by the sclera and vitreous, so defects in SLRP family members may contribute to myopia. The purpose of this study was to test whether mutations in the two members of the class III SLRPs, opticin (OPTC) and dermatan sulfate proteoglycan 3 (EPYC), are responsible for high myopia.<h4>Methods</h4>DNA was prepared from venous ...[more]
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Project description:ImportanceUncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets.ObjectiveTo assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia.Design, setting, and participantsThis genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020.ExposuresFour refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry.Main outcomes and measuresOdds ratios (ORs) of polygenic risk scores in replication samples.ResultsA total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16).Conclusions and relevanceGenetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.
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