Polygenic Risk for Type 2 Diabetes in African Americans
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Polygenic Risk for Type 2 Diabetes in African Americans. / 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.
In: Diabetes, Vol. 73, No. 6, 2024, p. 993-1001.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Polygenic Risk for Type 2 Diabetes in African Americans
AU - Irvin, Marguerite R.
AU - Ge, Tian
AU - Patki, Amit
AU - Srinivasasainagendra, Vinodh
AU - Armstrong, Nicole D.
AU - Davis, Brittney
AU - Jones, Alana C.
AU - Perez, Emma
AU - Stalbow, Lauren
AU - Lebo, Matthew
AU - Kenny, Eimear
AU - Loos, Ruth J.F.
AU - Ng, Maggie C.Y.
AU - Smoller, Jordan W.
AU - Meigs, James B.
AU - Lange, Leslie A.
AU - Karlson, Elizabeth W.
AU - Limdi, Nita A.
AU - Tiwari, Hemant K.
N1 - Publisher Copyright: © 2024 by the American Diabetes Association.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.2337/db23-0232
DO - 10.2337/db23-0232
M3 - Journal article
C2 - 38470993
AN - SCOPUS:85194013568
VL - 73
SP - 993
EP - 1001
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 6
ER -
ID: 395391957