Back to Search
Start Over
Genome-wide polygenic risk score for retinopathy of type 2 diabetes.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2021 May 29; Vol. 30 (10), pp. 952-960. - Publication Year :
- 2021
-
Abstract
- Diabetic retinopathy (DR) is a common consequence in type 2 diabetes (T2D) and a leading cause of blindness in working-age adults. Yet, its genetic predisposition is largely unknown. Here, we examined the polygenic architecture underlying DR by deriving and assessing a genome-wide polygenic risk score (PRS) for DR. We evaluated the PRS in 6079 individuals with T2D of European, Hispanic, African and other ancestries from a large-scale multi-ethnic biobank. Main outcomes were PRS association with DR diagnosis, symptoms and complications, and time to diagnosis, and transferability to non-European ancestries. We observed that PRS was significantly associated with DR. A standard deviation increase in PRS was accompanied by an adjusted odds ratio (OR) of 1.12 [95% confidence interval (CI) 1.04-1.20; P = 0.001] for DR diagnosis. When stratified by ancestry, PRS was associated with the highest OR in European ancestry (OR = 1.22, 95% CI 1.02-1.41; P = 0.049), followed by African (OR = 1.15, 95% CI 1.03-1.28; P = 0.028) and Hispanic ancestries (OR = 1.10, 95% CI 1.00-1.10; P = 0.050). Individuals in the top PRS decile had a 1.8-fold elevated risk for DR versus the bottom decile (P = 0.002). Among individuals without DR diagnosis, the top PRS decile had more DR symptoms than the bottom decile (P = 0.008). The PRS was associated with retinal hemorrhage (OR = 1.44, 95% CI 1.03-2.02; P = 0.03) and earlier DR presentation (10% probability of DR by 4 years in the top PRS decile versus 8 years in the bottom decile). These results establish the significant polygenic underpinnings of DR and indicate the need for more diverse ancestries in biobanks to develop multi-ancestral PRS.<br /> (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Aged
Black People genetics
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 genetics
Diabetes Mellitus, Type 2 pathology
Diabetic Retinopathy complications
Diabetic Retinopathy genetics
Diabetic Retinopathy pathology
Hispanic or Latino genetics
Humans
Middle Aged
Multifactorial Inheritance genetics
Risk Assessment
Risk Factors
White People genetics
Diabetes Mellitus, Type 2 epidemiology
Diabetic Retinopathy epidemiology
Genetic Predisposition to Disease
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 30
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 33704450
- Full Text :
- https://doi.org/10.1093/hmg/ddab067