Genome-wide meta-analysis for severe diabetic retinopathy

Hum Mol Genet. 2011 Jun 15;20(12):2472-81. doi: 10.1093/hmg/ddr121. Epub 2011 Mar 26.


Diabetic retinopathy is a leading cause of blindness. The purpose of this study is to identify novel genetic loci associated with the sight threatening complications of diabetic retinopathy. We performed a meta-analysis of genome-wide association data for severe diabetic retinopathy as defined by diabetic macular edema or proliferative diabetic retinopathy in unrelated cases ascertained from two large, type I diabetic cohorts: the Genetics of Kidney in Diabetes (GoKinD) and the Epidemiology of Diabetes Intervention and Control Trial (EDIC) studies. Controls were other diabetic subjects in the cohort. A combined total of 2829 subjects (973 cases, 1856 controls) were studied on 2 543 887 single nucleotide polymorphisms (SNPs). Subjects with nephropathy were excluded in a sub-analysis of 281 severe retinopathy cases. We also performed an association analysis of 1390 copy number variations (CNVs) using tag SNPs. No associations were significant at a genome-wide level after correcting for multiple measures. The meta-analysis did identify several associations that can be pursued in future replication studies, including an intergenic SNP, rs476141, on chromosome 1 (P-value 1.2 × 10(-7)). The most interesting signal from the CNV analysis came from the sub-group analysis without nephropathy subjects and is rs10521145 (P-value 3.4 × 10(-6)) in the intron of CCDC101, a histone acetyltransferase. This SNP tags the copy number region CNVR6685.1 on chromosome 16 at 28.5 Mb, a gain/loss site. In summary, this study nominates several novel genetic loci associated with the sight-threatening complications of diabetic retinopathy and anticipates future large-scale consortium-based validation studies.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • DNA Copy Number Variations
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetic Retinopathy / etiology
  • Diabetic Retinopathy / genetics*
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genome-Wide Association Study
  • Humans
  • Phenotype*
  • Polymorphism, Single Nucleotide / genetics*