| Title: | Genome-wide polygenic risk score for retinopathy of type 2 diabetes |
| Journal: | Human Molecular Genetics |
| Published: | 10 Mar 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33704450/ |
| DOI: | https://doi.org/10.1093/hmg/ddab067 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165647 |
| Citations: | 16 (9 in last 2 years) as of 8 Aug 2024 |
Publication 12876
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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.</p>
14 Keywords
- Adult
- Aged
- Black People
- Diabetes Mellitus, Type 2
- Diabetic Retinopathy
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Hispanic or Latino
- Humans
- Middle Aged
- Multifactorial Inheritance
- Risk Assessment
- Risk Factors
- White People
14 Authors
- Iain S Forrest
- Kumardeep Chaudhary
- Ishan Paranjpe
- Ha My T Vy
- Carla Marquez-Luna
- Ghislain Rocheleau
- Aparna Saha
- Lili Chan
- Tielman Van Vleck
- Ruth J F Loos
- Judy Cho
- Louis R Pasquale
- Girish N Nadkarni
- Ron Do
1 Application
| Application ID | Title |
|---|---|
| 16218 | Dissecting the genetic and phenotypic architecture of cardiovascular disease |
Enabling scientific discoveries that improve human health