There have been extensive research efforts for more than a decade to understand the genetics of diabetic retinopathy. To date, linkage and candidate gene associations have failed to deliver definitive results. Despite this challenge, it is well accepted that the identification of genetic variants, thereby implicating genes and pathways involved in the pathogenesis of diabetic retinopathy, offers an important mechanism by which to generate new therapies and better prevent this disease. With the completion of the human genome project, as well as the HapMap project, and the availability of platforms like the Affymetrix 500k SNP chip combined with bioinformatic computational methods, it is now possible to identify genetic variants on a genome scale in a cost effective manner. The major limiting factor remains accessing large, well phenotypically characterized cohorts of patients. To this end, we have established collaborations to analyze two large populations of patients with retinopathy due to type 1 diabetes.
Specific Aim 1. To carry out a genome wide association study of SNPs in a cohort of type 1 diabetic subjects with severe eye disease and controls ascertained from the Genetics of Kidneys in Diabetes (GoKinD) study to map genes associated with diabetic retinopathy.
Specific Aim 2. To confirm significant findings from this genome wide association in a separate cohort of type 1 diabetic individuals with severe eye disease and controls ascertained from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR).
Specific Aim 3. To carry out fine-mapping studies in genes or regions showing association with diabetic retinopathy and perform detailed genotype-phenotype analyses. The relevance of this research to public health is that an understanding of the genetic basis of diabetic retinopathy should lead to novel treatments and methods for preventing this diabetic complication.
| Grassi, Michael A; Rao, Vidhya; Winkler, Kathryn P et al. (2014) Genetic variation is the major determinant of individual differences in leukocyte endothelial adhesion. PLoS One 9:e87883 |
| Wang, Ai Ling; Rao, Vidhya R; Chen, Judy J et al. (2014) Role of FAM18B in diabetic retinopathy. Mol Vis 20:1146-59 |
| Grassi, Michael A; Sun, Wanjie; Gangaputra, Sapna et al. (2013) Validity of self-report in type 1 diabetic subjects for laser treatment of retinopathy. Ophthalmology 120:2580-2586 |
| Grassi, Michael A; Tikhomirov, Anna; Ramalingam, Sudha et al. (2012) Replication analysis for severe diabetic retinopathy. Invest Ophthalmol Vis Sci 53:2377-81 |
| Kiernan, Daniel F; Shah, Rohan J; Hariprasad, Seenu M et al. (2011) Thirty-Year follow-up of an African American family with macular dystrophy of the retina, locus 1 (North Carolina macular dystrophy). Ophthalmology 118:1435-43 |
| Cao, Dingcai; Pokorny, Joel; Grassi, Michael A (2011) Isolated mesopic rod and cone electroretinograms realized with a four-primary method. Doc Ophthalmol 123:29-41 |
| Grassi, Michael A; Tikhomirov, Anna; Ramalingam, Sudha et al. (2011) Genome-wide meta-analysis for severe diabetic retinopathy. Hum Mol Genet 20:2472-81 |
| Grassi, Michael A; Mazzulla, D Anthony; Knudtson, Michael D et al. (2009) Patient self-report of prior laser treatment reliably indicates presence of severe diabetic retinopathy. Am J Ophthalmol 147:501-4 |
