Polygenic Risk for Type 2 Diabetes in African Americans

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Documents

  • Marguerite R. Irvin
  • Tian Ge
  • Amit Patki
  • Vinodh Srinivasasainagendra
  • Nicole D. Armstrong
  • Brittney Davis
  • Alana C. Jones
  • Emma Perez
  • Lauren Stalbow
  • Matthew Lebo
  • Eimear Kenny
  • Loos, Ruth
  • Maggie C.Y. Ng
  • Jordan W. Smoller
  • James B. Meigs
  • Leslie A. Lange
  • Elizabeth W. Karlson
  • Nita A. Limdi
  • Hemant K. Tiwari

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 (R2) 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,ingeneral, 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.

Original languageEnglish
JournalDiabetes
Volume73
Issue number6
Pages (from-to)993-1001
Number of pages9
ISSN0012-1797
DOIs
Publication statusPublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 by the American Diabetes Association.

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