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Polygenic Risk for Type 2 Diabetes in African Americans
Marguerite R Irvin1, Tian Ge2,3,4,5, Amit Patki6
1Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.
Diabetes
|March 12, 2024
Summary
A new polygenic risk score (PRS) for type 2 diabetes (T2D) was developed and optimized for African Americans (AAs). This PRSAA demonstrated significant prediction of T2D risk in AA populations.
Area of Science:
- Genetics
- Epidemiology
- Precision Medicine
Background:
- African Americans (AAs) are underrepresented in polygenic risk score (PRS) studies.
- Type 2 diabetes (T2D) disproportionately affects AA populations, highlighting the need for tailored risk prediction tools.
Purpose of the Study:
- To develop and validate an AA-focused T2D PRS (PRSAA) using a large dataset of African Americans.
- To evaluate the performance of the PRSAA compared to existing T2D PRS in independent AA cohorts.
Main Methods:
- Integrated genome-wide data from multiple observational studies (N=101,987 AAs) to train the PRSAA using Bayesian polygenic modeling.
- Tested the PRSAA in three independent studies (N=7,275 AAs) and compared its predictive performance against other T2D PRS.
Main Results:
- A 1-SD increase in PRSAA was associated with a 40-60% increased odds of T2D across testing cohorts (ORs ranging from 1.40 to 1.60).
- The PRSAA captured 1.0-2.6% of the T2D liability variance, with positive predictive values ranging from 14-35% at top thresholds.
- PRSAA performance was comparable to existing T2D PRS in the studied AA populations.
Conclusions:
- The developed PRSAA shows utility in predicting T2D risk within the African American population.
- Further research with larger datasets is needed to fully evaluate and refine within-ancestry PRS for AAs.
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