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Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia.

Publication ,  Journal Article
Khor, CC; Miyake, M; Chen, LJ; Shi, Y; Barathi, VA; Qiao, F; Nakata, I; Yamashiro, K; Zhou, X; Tam, POS; Cheng, C-Y; Tai, ES; Vithana, EN ...
Published in: Hum Mol Genet
December 20, 2013

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 × 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 × 10(-10), per-allele odds ratio (OR) = 1.26 for rs13382811 and P = 2.01 × 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.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 20, 2013

Volume

22

Issue

25

Start / End Page

5288 / 5294

Location

England

Related Subject Headings

  • Zinc Finger E-box Binding Homeobox 2
  • Sclera
  • Retina
  • Repressor Proteins
  • Polymorphism, Single Nucleotide
  • Myopia
  • Mice
  • Humans
  • Homeodomain Proteins
  • Genome-Wide Association Study
 

Citation

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Khor, C. C., Miyake, M., Chen, L. J., Shi, Y., Barathi, V. A., Qiao, F., … Yoshimura, N. (2013). Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia. Hum Mol Genet, 22(25), 5288–5294. https://doi.org/10.1093/hmg/ddt385
Khor, Chiea Chuen, Masahiro Miyake, Li Jia Chen, Yi Shi, Veluchamy A. Barathi, Fan Qiao, Isao Nakata, et al. “Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia.Hum Mol Genet 22, no. 25 (December 20, 2013): 5288–94. https://doi.org/10.1093/hmg/ddt385.
Khor CC, Miyake M, Chen LJ, Shi Y, Barathi VA, Qiao F, et al. Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia. Hum Mol Genet. 2013 Dec 20;22(25):5288–94.
Khor, Chiea Chuen, et al. “Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia.Hum Mol Genet, vol. 22, no. 25, Dec. 2013, pp. 5288–94. Pubmed, doi:10.1093/hmg/ddt385.
Khor CC, Miyake M, Chen LJ, Shi Y, Barathi VA, Qiao F, Nakata I, Yamashiro K, Zhou X, Tam POS, Cheng C-Y, Tai ES, Vithana EN, Aung T, Teo Y-Y, Wong T-Y, Moriyama M, Ohno-Matsui K, Mochizuki M, Matsuda F, Nagahama Study Group, Yong RYY, Yap EPH, Yang Z, Pang CP, Saw S-M, Yoshimura N. Genome-wide association study identifies ZFHX1B as a susceptibility locus for severe myopia. Hum Mol Genet. 2013 Dec 20;22(25):5288–5294.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 20, 2013

Volume

22

Issue

25

Start / End Page

5288 / 5294

Location

England

Related Subject Headings

  • Zinc Finger E-box Binding Homeobox 2
  • Sclera
  • Retina
  • Repressor Proteins
  • Polymorphism, Single Nucleotide
  • Myopia
  • Mice
  • Humans
  • Homeodomain Proteins
  • Genome-Wide Association Study