Genetic variants at 13q12.12 are associated with high myopia in the Han Chinese population

Am J Hum Genet. 2011 Jun 10;88(6):805-813. doi: 10.1016/j.ajhg.2011.04.022. Epub 2011 Jun 6.

Abstract

High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10(-4) in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10(-16), heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10(-11) to 6.16 × 10(-16). This associated locus contains three genes-MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / genetics
  • Asian Continental Ancestry Group / genetics
  • China / ethnology
  • Chromosomes, Human, Pair 13 / genetics*
  • Female
  • Gene Expression
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Glycoproteins / genetics
  • Humans
  • Male
  • Metalloendopeptidases / genetics
  • Myopia / ethnology
  • Myopia / genetics*
  • Polymorphism, Single Nucleotide
  • Retina / metabolism
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins

Substances

  • Adiponectin
  • C1QTNF9B protein, human
  • Glycoproteins
  • Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
  • Metalloendopeptidases
  • mitochondrial intermediate peptidase