학술논문
Polygenic Risk for Type 2 Diabetes in African Americans.
Document Type
Academic Journal
Author
Irvin MR; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.; Ge T; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA.; Department of Psychiatry, Massachusetts General Hospital, Boston, MA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.; Patki A; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.; Srinivasasainagendra V; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.; Armstrong ND; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.; Davis B; Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.; Jones AC; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.; Perez E; Department of Medicine, Brigham and Women's Hospital, Boston, MA.; Mass General Brigham Personalized Medicine, Boston, MA.; Stalbow L; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.; Lebo M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.; Mass General Brigham Personalized Medicine, Boston, MA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA.; Kenny E; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY.; Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.; Loos RJF; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.; The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine, University of Copenhagen, Copenhagen, Denmark.; Ng MCY; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN.; Smoller JW; Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA.; Department of Psychiatry, Massachusetts General Hospital, Boston, MA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.; Meigs JB; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA.; Department of Medicine, Massachusetts General Hospital, Boston, MA.; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA.; Lange LA; Department of Epidemiology, University of Colorado School of Public Health, Aurora, CO.; Karlson EW; Department of Medicine, Brigham and Women's Hospital, Boston, MA.; Mass General Brigham Personalized Medicine, Boston, MA.; Limdi NA; Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL.; Tiwari HK; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL.
Source
Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
Subject
Language
English
Abstract
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, in general, 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.
(© 2024 by the American Diabetes Association.)
(© 2024 by the American Diabetes Association.)