title: Genome-wide meta-analysis for severe diabetic retinopathy.
abstract: 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.
authors: Section of Ophthalmology and Visual Science, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors: Michael A
authors: MA
authors: Grassi
authors: Anna
authors: A
authors: Tikhomirov
authors: Sudha
authors: S
authors: Ramalingam
authors: Jennifer E
authors: JE
authors: Below
authors: Nancy J
authors: NJ
authors: Cox
authors: Dan L
authors: DL
authors: Nicolae
mesh_terms: D015331:Cohort Studies; D056915:DNA Copy Number Variations; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000209:etiology / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*