Genetic prediction of myopia in different ethnic ancestries

Abstract

Purpose. Myopia has been shown to have a complex mode of inheritance, being influenced by both genetic and environ- mental factors. Here, an introduction into myopia genetics is given, with the shortcomings of current genetic prediction for myopia discussed, including the proportionally limited research on genetic prediction in people of non-European ancestry. A previously developed genetic risk score derived from European participants was evaluated in participants of non-European ancestry. Methods. Participants from UK Biobank who self-reported their ethnicity as “Asian”, “Chinese”, or “Black” and who had refractive error and genetic data available were included in the analysis. Ancestral homogeneity was confirmed using principal component analysis, resulting in samples of 3500 Asian, 444 Chinese, and 3132 Black participants. A published refractive error GWAS meta-analysis of 711,984 participants of European ancestry was used to create a weighted genetic risk score model which was then applied to participants from each ethnic group. Accuracy of genetic prediction of refractive error was estimated as the proportion of variance explained (PVE). Receiver operating characteristic (ROC) curves were developed to estimate myopia prediction performance at three thresholds: any myopia (equal to or more than 0.75D), moderate myopia (between −3.00D and −4.99D) and high myopia (equal to or more than −5.00D). Odds ratios for myo- pia were calculated for the participants in the top 10th or 5th percentile of genetic risk score distribution, comparing them to the remainder of the population. Results. The PVE value for refractive error was 6.4 %, 6.2 %, and 1.5 % for those with Asian, Chinese and Black ethnicity, respectively (compared to 11.2 % in Europeans). Odds ra- tios for any myopia and moderate myopia development for those within the top 10th and 5th percentile of genetic risk were significant in all ethnic groups (P < 0.05). However, the genetic risk score was not able to reliably identify those at risk of high myopia, other than for participants of Chinese ethnicity (P < 0.05). Conclusion. Prediction of refractive error in Asian, Chinese and Black participants was ~ 57 %, 55 % and 13 % as accurate in comparison to prediction in European participants. Further research in diverse ethnic populations is needed to improve prediction accuracy. Keywords Myopia, Genetic Prediction, Refractive Error, Polygenic Risk Score