Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Nat Commun. 2015 Mar 31:6:6689. doi: 10.1038/ncomms7689.

Abstract

Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, Pmeta=3.9 × 10(-13)) and corneal curvature (Pmeta=2.9 × 10(-40)) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR)meta=1.13, Pmeta=0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Asian People / genetics
  • Cohort Studies
  • Cornea / metabolism*
  • Disease Models, Animal
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Middle Aged
  • Myopia / genetics*
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism*
  • Retina / metabolism*
  • Severity of Illness Index
  • White People / genetics
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • Young Adult

Substances

  • Proto-Oncogene Proteins
  • RNA, Messenger
  • WNT7B protein, human
  • Wnt Proteins
  • Wnt7b protein, mouse