Genome-wide association studies in Asians confirm the involvement of ATOH7 and TGFBR3, and further identify CARD10 as a novel locus influencing optic disc area

Hum Mol Genet. 2011 May 1;20(9):1864-72. doi: 10.1093/hmg/ddr060. Epub 2011 Feb 9.

Abstract

Damage to the optic nerve (e.g. from glaucoma) has an adverse and often irreversible impact on vision. Earlier studies have suggested that the size of the optic nerve head could be governed by hereditary factors. We conducted a genome-wide association study (GWAS) on 4445 Singaporean individuals (n = 2132 of Indian and n = 2313 of Malay ancestry, respectively), with replication in Rotterdam, the Netherlands (n = 9326 individuals of Caucasian ancestry) using the most widely reported parameter for optic disc traits, the optic disc area. We identified a novel locus on chromosome 22q13.1, CARD10, which strongly associates with optic disc area in both Singaporean cohorts as well as in the Rotterdam Study (RS; rs9607469, per-allele change in optic disc area = 0.051 mm(2); P(meta) = 2.73×10(-12)) and confirmed the association between CDC7/TGFBR3 (lead single nucleotide polymorphism (SNP) rs1192415, P(meta) = 7.57×10(-17)) and ATOH7 (lead SNP rs7916697, P(meta) = 2.00 × 10(-15)) and optic disc area in Asians. This is the first Asian-based GWAS on optic disc area, identifying a novel locus for the optic disc area, but also confirming the results found in Caucasian persons suggesting that there are general genetic determinants applicable to the size of the optic disc across different ethnicities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian Continental Ancestry Group / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • CARD Signaling Adaptor Proteins / genetics*
  • CARD Signaling Adaptor Proteins / metabolism
  • Chromosomes, Human, Pair 22 / genetics
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Glaucoma / ethnology
  • Glaucoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Optic Disk / chemistry*
  • Optic Disk / metabolism
  • Polymorphism, Single Nucleotide
  • Proteoglycans / genetics*
  • Proteoglycans / metabolism
  • Receptors, Transforming Growth Factor beta / genetics*
  • Receptors, Transforming Growth Factor beta / metabolism

Substances

  • ATOH7 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • CARD Signaling Adaptor Proteins
  • CARD10 protein, human
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • betaglycan