Genome-wide association study of diabetic retinopathy in a Taiwanese population

Ophthalmology. 2011 Apr;118(4):642-8. doi: 10.1016/j.ophtha.2010.07.020. Epub 2011 Feb 18.


Purpose: Diabetic retinopathy (DR) is a microvascular complication of diabetes with a complex multifactorial pathogenesis. The aim of this study was to identify the susceptibility genes that increase the risk of DR in type 2 diabetes (T2D) and to further elucidate the underlying mechanism of DR pathogenesis.

Design: A case-control study.

Participants: We included 749 unrelated individuals with T2D (174 with DR and 575 without DR) and 100 nondiabetic controls.

Methods: We conducted a genome-wide association study using Illumina HumanHap550-Duo BeadChips.

Main outcome measures: Compared with the genotypic distribution of single nucleotide polymorphisms (SNPs) between subjects with DR and without DR.

Results: Using statistical models, we selected a total of 12 SNPs with P-values <1 × 10(-6) that were associated with DR. After controlling for diabetes duration and hemoglobin A(1C), 9 of the 12 SNPs located on 5 chromosomal regions were found to be associated with DR. Five loci not previously associated with DR susceptibility were identified in and around the following genes: MYSM1 (Myb-like, SWIRM, and MPN domains 1) located on chromosome 1p (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.03-2.20); PLXDC2 (plexin domain-containing 2) located on the chromosome 10p (OR, 1.67; 95% CI, 1.06-2.65); ARHGAP22 (Rho GTPase-activating protein 22) located on chromosome 10q (OR, 1.65; 95% CI, 1.05-2.60); and HS6ST3 (heparan sulfate 6-O-sulfotransferase 3) located on chromosome 13q (OR, 2.33; 95% CI, 1.13-4.77). The SNPs rs13163610 and rs17376456 located in the unknown gene on chromosome 5q were also associated with DR (OR, 3.63; 95% CI, 1.38-9.58).

Conclusions: We identified a genetic association for susceptibility to DR in 5 novel chromosomal regions and PLXDC2 and ARHGAP22, the latter 2 of which are genes implicated in endothelial cell angiogenesis and increased capillary permeability. These findings suggest unsuspected pathways in the pathogenesis of DR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Pressure
  • Case-Control Studies
  • Chimerin 1 / genetics*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetic Retinopathy / genetics*
  • Eye Proteins / genetics
  • Female
  • Gene Expression Profiling
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / genetics*
  • Surveys and Questionnaires
  • Taiwan


  • Chimerin 1
  • Eye Proteins
  • Glycated Hemoglobin A
  • PLXDC2 protein, human
  • Receptors, Cell Surface