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- Title
Polygenic Risk for Type 2 Diabetes in African Americans.
- Authors
Irvin, Marguerite R.; Ge, Tian; Patki, Amit; Srinivasasainagendra, Vinodh; Armstrong, Nicole D.; Davis, Brittney; Jones, Alana C.; Perez, Emma; Stalbow, Lauren; Lebo, Matthew; Kenny, Eimear; Loos, Ruth J.F.; Ng, Maggie C.Y.; Smoller, Jordan W.; Meigs, James B.; Lange, Leslie A.; Karlson, Elizabeth W.; Limdi, Nita A.; Tiwari, Hemant K.
- Abstract
African Americans (AAs) have been underrepresented in polygenic risk score (PRS) studies. Here, we integrated genome-wide data from multiple observational studies on type 2 diabetes (T2D), encompassing a total of 101,987 AAs, to train and optimize an AA-focused T2D PRS (PRSAA), using a Bayesian polygenic modeling method. We further tested the score in three independent studies with a total of 7,275 AAs and compared the PRSAA with other published scores. Results show that a 1-SD increase in the PRSAA was associated with 40–60% increase in the odds of T2D (odds ratio [OR] 1.60, 95% CI 1.37–1.88; OR 1.40, 95% CI 1.16–1.70; and OR 1.45, 95% CI 1.30–1.62) across three testing cohorts. These models captured 1.0–2.6% of the variance (R 2) in T2D on the liability scale. The positive predictive values for three calculated score thresholds (the top 2%, 5%, and 10%) ranged from 14 to 35%. The PRSAA, in general, performed similarly to existing T2D PRS. The need remains for larger data sets to continue to evaluate the utility of within-ancestry scores in the AA population. Article Highlights: This study aimed to better understand the performance of existing and a novel polygenic risk scores (PRS) for type 2 diabetes in African American (AA) populations. A PRS was developed using only genetic data from AA populations (PRSAA) and compared with scores developed using genetic data from other ancestral populations. The performance metrics of the PRSAA were comparable to a published multiancestry PRS developed using training data from much larger study samples. The utility of single-ancestry PRS in AAs should be reevaluated when larger AA training data sets are available.
- Subjects
GENETIC risk score; TYPE 2 diabetes; MONOGENIC &; polygenic inheritance (Genetics); AFRICAN Americans; ODDS ratio
- Publication
Diabetes, 2024, Vol 73, Issue 6, p993
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db23-0232