Polygenic Risk for Type 2 Diabetes in African Americans

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dokumenter

  • 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.

OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind73
Udgave nummer6
Sider (fra-til)993-1001
Antal sider9
ISSN0012-1797
DOI
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
The eMERGE Network was initiated and funded by National Human Genome Research Institute through the following grants: U01HG006828 (Cincinnati Children\u2019s Hospital Medical Center and Boston Children\u2019s Hospital), U01HG006830 (Children\u2019s 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 National Human Genome Research Institute through U01HG008685, the Columbia University site was funded through U01HG008680, and the University of Alabama site was funded through National Human Genome Research Institute (U01HG011167). This work was additionally supported by the Doris Duke Charitable Foundation grant 2020096 to A.L. and by the following National Institutes of Health grants: National Center for Advancing Translational Sciences, UL1TR001873; The New England Precision Medicine Consortium of the All of Us Research Program, OT2OD026553; National Heart, Lung, and Blood Institute, OT2HL161841, R01HL151855 (J.B.M.), and R01HL092173 (N.A.L.); National Institute of Arthritis and Musculoskeletal and Skin Diseases, P30AR070253, P30AR069625, R01AR063759 (E.W.K.), and R21AR078339 (E.W.K.); National Human Genome Research Institute, U01HG011723 and R01HG012354 (T.G.); and National Institute of Diabetes and Digestive and Kidney Diseases, U01DK105556 (M.C.Y.N.), R01DK066358 (M.C.Y.N.), R01DK078616 (J.B.M.), and K25DK128563 (A.K.). The University of Alabama at Birmingham (UAB) cohorts were funded through the following grants: National Heart, Lung, and Blood Institute supported the REGARDS genetics (R01HL136666), HyperGEN (R01HL055673), GenHAT (R01HL123782), and WPC (R01HL092173 and K24HL133373) studies. The parent REGARDS study is supported by the National Institute of Neurological Disorders and Stroke cooperative agreement U01NS041588 co-funded by the National Institute on Aging, the National Institutes of Health, and the Department of Health and Human Services. M.R.I. was further supported by National Heart and Lung Institute R35HL155466. Duality of Interest.

Funding Information:
Acknowledgments. The authors used dbGaP accession number phs001672.v11.p1. to retrieve the summary statistics data. The authors thank Million Veteran Program (MVP) staff, researchers, and volunteers, who contributed to MVP, and especially participants who previously served their country in the military and now generously agreed to enroll in the study (see https://www.research.va.gov/mvp/ for more details). Funding. The eMERGE Network was initiated and funded by National Human Genome Research Institute through the following grants: U01HG006828 (Cincinnati Children\u2019s Hospital Medical Center and Boston Children\u2019s Hospital), U01HG006830 (Children\u2019s 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 (North-western 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 National Human Genome Research Institute through U01HG008685, the Columbia University site was funded through U01HG008680, and the University of Alabama site was funded through National Human Genome Research Institute (U01HG011167). This work was additionally supported by the Doris Duke Charitable Foundation grant 2020096 to A.L. and by the following National Institutes of Health grants: National Center for Advancing Translational Sciences, UL1TR001873; The New England Precision Medicine Consortium of the All of Us Research Program, OT2OD026553; National Heart, Lung, and Blood Institute, OT2HL161841, R01HL151855 (J.B.M.), and R01HL092173 (N.A.L.); National Institute of Arthritis and Musculoskeletal and Skin Diseases, P30AR070253, P30AR069625, R01AR063759 (E.W.K.), and R21AR078339 (E.W.K.); National Human Genome Research Institute, U01HG011723 and R01HG012354 (T.G.); and National Institute of Diabetes and Digestive and Kidney Diseases, U01DK105556 (M.C.Y.N.), R01DK066358 (M.C.Y.N.), R01DK078616 (J.B.M.), and K25DK128563 (A.K.). The University of Alabama at Birmingham (UAB) cohorts were funded through the following grants: National Heart, Lung, and Blood Institute supported the REGARDS genetics (R01HL136666), HyperGEN (R01HL055673), GenHAT (R01HL123782), and WPC (R01HL092173 and K24HL133373) studies. The parent REGARDS study is supported by the National Institute of Neurological Disorders and Stroke cooperative agreement U01NS041588 co-funded by the National Institute on Aging, the National Institutes of Health, and the Department of Health and Human Services. M.R.I. was further supported by National Heart and Lung Institute R35HL155466. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. M.R.I. and B.D. contributed to writing the original draft and visualization. T.G. contributed to writing, reviewing, and editing the manuscript and to methodology and investigation. A.P. contributed to the investigation. V.S., N.D.A., A.C.J., E.P., and L.S. contributed to the methodology and investigation. M.L., E.K., R.J.F.L., M.C.Y.N., and L.A.L. contributed to writing, reviewing, and editing the manuscript. J.W.S., J.B.M., and E.W.K. contributed to writing, reviewing, and editing the manuscript, study conceptualization, methodology, and investigation. N.A.L. contributed to writing, reviewing, and editing the manuscript and to methodology, study conceptualization, and funding acquisition. H.K.T. contributed to writing, reviewing, and editing the manuscript, study conceptualization, and funding acquisition. M.R.I. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Publisher Copyright:
© 2024 by the American Diabetes Association.

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