Diabetic retinopathy is caused by chronic exposure of the retinal tissue to glucose owing to uncontrolled or poorly controlled diabetes. It is a leading cause of sight-threatening blindness among adults with diabetes, with significant morbidity among those who need to manage early stages of this disease. It has lifelong consequences for those living with diabetes, and the financial burden of its treatment is immense. We propose to capitalize on the endogamous structure of the population in Chennai, India, to map common and rare susceptibility loci. We will leverage the existing infrastructure for standardized data collection, with multifaceted phenotyping of diabetic retinopathy, established by the SN DREAMS project at the Vision Research Center, in Sankara Nethralaya. Focusing on proliferative disease, and diabetic macular edema, we will examine genetic variation in retinopathy cases and diabetic controls without retinopathy using the cosmopolitan MEG array, and S. Indian-specific imputation of markers using a variety of public and private data. We propose to conduct extensive modeling of covariates, such as HbA1C, and lipid levels, in an effort to account for the architecture of the exposures. We will also target consanguineous families for whole genome sequencing in order to find genes for diabetic retinopathy, utilizing identity-by-descent sharing and the endogamous population structure with its unique haplotype structures. This project will enable us to better define the genetic architecture of diabetic retinopathy in India, and worldwide.

Public Health Relevance

Diabetic retinopathy is a devastating eye disease that occurs in individuals with diabetes, due to prolonged glucose exposure. The major known independent risk factors associated with predisposition to diabetic retinopathy are longer duration of diabetes, higher glycosylated hemoglobin (HbA1c levels), insulin use and higher systolic blood pressure, but this disease shows greater genetic predisposition in some individuals. We propose to capitalize on the endogamous structure of the population in Chennai, India, to map common and rare susceptibility loci, filling significant gaps in the knowledge about its genetic architecture.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY027134-01A1
Application #
9390598
Study Section
Kidney, Nutrition, Obesity and Diabetes (KNOD)
Program Officer
Shen, Grace L
Project Start
2017-09-30
Project End
2020-08-31
Budget Start
2017-09-30
Budget End
2018-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106