Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia
Publication in refereed journal


摘要Severe myopia (defined as spherical equivalent <-6.0 D) is a predominant problem in Asian countries, resulting in substantial morbidity. We performed a meta-analysis of four genome-wide association studies (GWAS), all of East Asian descent totaling 1603 cases and 3427 controls. Two single nucleotide polymorphisms (SNPs) (rs13382811 from ZFHX1B [encoding for ZEB2] and rs6469937 from SNTB1) showed highly suggestive evidence of association with disease (P < 1 x 10(-7)) and were brought forward for replication analysis in a further 1241 severe myopia cases and 3559 controls from a further three independent sample collections. Significant evidence of replication was observed, and both SNP markers surpassed the formal threshold for genome-wide significance upon meta-analysis of both discovery and replication stages (P = 5.79 x 10(-10), per-allele odds ratio (OR) = 1.26 for rs13382811 and P = 2.01 x 10(-9), per-allele OR = 0.79 for rs6469937). The observation at SNTB1 is confirmatory of a very recent GWAS on severe myopia. Both genes were expressed in the human retina, sclera, as well as the retinal pigmented epithelium. In an experimental mouse model for myopia, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for Zfhx1b and Sntb1. These new data advance our understanding of the molecular pathogenesis of severe myopia.
著者Khor CC, Miyake M, Chen LJ, Shi Y, Barathi VA, Qiao F, Nakata I, Yamashiro K, Zhou X, Tam POS, Cheng CY, Tai ES, Vithana EN, Aung T, Teo YY, Wong TY, Moriyama M, Ohno-Matsui K, Mochizuki M, Matsuda F, Yong RYY, Yap EPH, Yang ZL, Pang CP, Saw SM, Yoshimura N
期刊名稱Human Molecular Genetics
出版社Oxford University Press (OUP): Policy B - Oxford Open Option B
頁次5288 - 5294
Web of Science 學科類別Biochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Genetics & Heredity; GENETICS & HEREDITY

上次更新時間 2021-14-01 於 23:32