Newly identified genes for refractive error and risk of myopia

Abstract

Purpose : Myopia is widely recognized as a multifactorial, complex genetic disorder. Recently, More than 100 loci for refractive phenotypes were identified by the Consortium for Refractive Error and Myopia (CREAM) and 23andMe. We aimed to assess the overall risk of refractive error for carriership of the associated variants by using polygenic risk scores.

Methods : We performed our analyses in the population-based Rotterdam Study I-III (RS I-III; n = 10,792) and in the high myopia case control study MYST (n = 1165). Polygenic risk scores were calculated using the P-values and Z-scores from the meta-analysis of CREAM and 23andMe excluding RS I-III (n = 149,628). SNPs were selected on imputation quality score > 0.8 and MAF > 0.01. We performed P-value-informed clumping using PLINK. For each individual, scores were calculated based on a range of P-value thresholds. We calculated the variance explained by the polygenic risk scores using regression analyses. Mean odds ratios of myopia were calculated per decile of genetic risk score, using the 5^th decile as the reference.

Results : A total of 243,938 SNPs was available for these analyses. The maximum variance of SE explained was 7.9% in RS I-III and 2.7% in MYST, at a P-value threshold of 0.005 including 7,307 variants. Risk scores ranged from a mean risk score of 0.06 (SD 0.006) in the lowest risk score category to 0.01 (SD 0.006) in the highest risk score category. The lowest and the highest decile of genetic risk were associated with OR 0.23 (95% CI = 0.15-0.36), and OR 9.10 (95% CI = 5.91-14.01) of myopia, respectively.

Conclusions : The current genetic findings discriminate well between subjects with low and high risk of myopia. Nevertheless, the explained variance is low, indicating that the missing heritability is still significant.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.