Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design. (January 2022)

• Record Type: Journal Article
• Authors: Han, Xiaotong; Liu, Tianzi; Ding, Xiaohu; Liu, Jialin; Lin, Xingyan; Wang, Decai; Riaz, Moeen; Baird, Paul N.; Xie, Zhi; Cheng, Yuan; Li, Yi; Mori, Yuki; Miyake, Masahiro; Li, Hengtong; Cheng, Ching-Yu; Zeng, Changqing; Ohno-Matsui, Kyoko; Zhou, Xiangtian; Liu, Fan; He, Mingguang
• Is Part Of: Journal of genetics and genomics. Volume 49:Number 1(2022)
• Page Start: 54
• Page End: 62
• Publication Date: 2022-01
• Subjects: Extreme phenotype -- Genome-wide association study -- Population heterogeneity -- Refractive error -- East Asian population -- Prediction; Genetics -- Periodicals; Genomics -- Periodicals; 576.505
• DOI: 10.1016/j.jgg.2021.08.011
• Languages: English
• ISSNs: 1673-8527

Abstract

Abstract: The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies (GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent (SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou (631 < −6.00D and 574 > 0.00D) and Wenzhou (593 < −6.00D and 54 > −1.75D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1q25.2 FAM163A, 10p11.22 NRP1 / PRAD3, and 10p11.21 ANKRD30A / MTRNR2L7, together explaining 3.34% of SE variance. 10p11.21 is successfully replicated. The allele frequencies of all three loci show significant differences between major continental groups ( P < 0.001). The SE reducing (more myopic) allele of rs10913877 (1q25.2 FAM163A ) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans (EAS = 0.60, EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19 . These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.