title: Genome-wide association study of diabetic retinopathy in a Taiwanese population.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A case-control study.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Huang
authors.forename: Jane-Ming
authors.initials: JM
authors.lastname: Lin
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Lin
authors.forename: Ching-Chu
authors.initials: CC
authors.lastname: Chen
authors.forename: Shih-Yin
authors.initials: SY
authors.lastname: Chen
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D001794:Blood Pressure; D016022:Case-Control Studies; D020848:Chimerin 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D003930:Diabetic Retinopathy / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D011795:Surveys and Questionnaires; D013624:Taiwan
chemical_list: D020848:Chimerin 1; D005136:Eye Proteins; D006442:Glycated Hemoglobin; D011956:Receptors, Cell Surface; C558538:PLXDC2 protein, human