African Americans (AAs) have been underrepresented in polygenic risk score (PRS) studies. Herein, 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 (PRS-CS). We further tested the score in three independent studies with a total of 7,275 AAs. We then compared the PRSAA to other published scores. Results show that a 1 standard deviation increase in the PRSAA was associated with 40%-60% increase in the odds of T2D (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 (PPV) for three calculated score thresholds (the top 2%, 5% 10%) ranged from 14% to 35%. The PRSAA, in general, performed similarly to existing T2D PRS. . Larger datasets remain needed to continue to evaluate the utility of within-ancestry scores in the AA population.
Funding
The eMERGE Network was initiated and funded by National Human Genome Research Institute (NHGRI) through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center and Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health, Marshfield Clinic Research Foundation, and Pennsylvania State University); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative and the University of Washington); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). The eMERGE IV Mass General Brigham site was funded by the NHGRI through U01HG008685, the Columbia University site was funded through U01HG008680, and the University of Alabama site was funded through U01HG011167. This work was additionally supported by grant 2020096 from the Doris Duke Charitable Foundation (A.L.) and by the following NIH grants: UL1TR001873, OT2OD026553, OT2HL161841, P30AR070253, P30AR069625, U01HG011723, U01DK105556 (M.C.Y.N), R01DK066358 (M.C.Y.N), R01DK078616 (J.B.M.), R01HL151855 (J.B.M.), R01HL092173 (N.A.L.), R01AR063759 (E.W.K.), R21AR078339 (E.W.K), R01HG012354 (T.G.), K25DK128563 (A.K.), K23DK114551 (M.S.U).
