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Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations.
Ge, Tian; Irvin, Marguerite R; Patki, Amit; Srinivasasainagendra, Vinodh; Lin, Yen-Feng; Tiwari, Hemant K; Armstrong, Nicole D; Benoit, Barbara; Chen, Chia-Yen; Choi, Karmel W; Cimino, James J; Davis, Brittney H; Dikilitas, Ozan; Etheridge, Bethany; Feng, Yen-Chen Anne; Gainer, Vivian; Huang, Hailiang; Jarvik, Gail P; Kachulis, Christopher; Kenny, Eimear E; Khan, Atlas; Kiryluk, Krzysztof; Kottyan, Leah; Kullo, Iftikhar J; Lange, Christoph; Lennon, Niall; Leong, Aaron; Malolepsza, Edyta; Miles, Ayme D; Murphy, Shawn; Namjou, Bahram; Narayan, Renuka; O'Connor, Mark J; Pacheco, Jennifer A; Perez, Emma; Rasmussen-Torvik, Laura J; Rosenthal, Elisabeth A; Schaid, Daniel; Stamou, Maria; Udler, Miriam S; Wei, Wei-Qi; Weiss, Scott T; Ng, Maggie C Y; Smoller, Jordan W; Lebo, Matthew S; Meigs, James B; Limdi, Nita A; Karlson, Elizabeth W.
Afiliação
  • Ge T; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. tge1@mgh.harvard.edu.
  • Irvin MR; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA. tge1@mgh.harvard.edu.
  • Patki A; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. tge1@mgh.harvard.edu.
  • Srinivasasainagendra V; Broad Institute of MIT and Harvard, Cambridge, MA, USA. tge1@mgh.harvard.edu.
  • Lin YF; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Tiwari HK; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Armstrong ND; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Benoit B; Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
  • Chen CY; Department of Public Health & Medical Humanities, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Choi KW; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
  • Cimino JJ; Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Davis BH; Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Dikilitas O; Mass General Brigham Research Information Science & Computing, Boston, MA, USA.
  • Etheridge B; Translational Biology, Biogen Inc., Cambridge, MA, USA.
  • Feng YA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Gainer V; Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
  • Huang H; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
  • Jarvik GP; Informatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Kachulis C; Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Kenny EE; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
  • Khan A; Department of Internal Medicine, Mayo Clinician-Investigator Training Program, Mayo Clinic, Rochester, MN, USA.
  • Kiryluk K; Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Kottyan L; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Kullo IJ; Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
  • Lange C; Mass General Brigham Research Information Science & Computing, Boston, MA, USA.
  • Lennon N; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Leong A; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Malolepsza E; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Miles AD; Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Murphy S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Namjou B; Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Narayan R; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, USA.
  • O'Connor MJ; Division of Nephrology, Department of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, USA.
  • Pacheco JA; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Perez E; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
  • Rasmussen-Torvik LJ; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Rosenthal EA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Schaid D; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stamou M; Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Udler MS; Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Wei WQ; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Weiss ST; Informatics Institute, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Ng MCY; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Smoller JW; Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
  • Lebo MS; Department of Neurology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
  • Meigs JB; UMass Memorial Health Care, Worcester, MA, USA.
  • Limdi NA; Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Karlson EW; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Genome Med ; 14(1): 70, 2022 06 29.
Article em En | MEDLINE | ID: mdl-35765100
ABSTRACT

BACKGROUND:

Type 2 diabetes (T2D) is a worldwide scourge caused by both genetic and environmental risk factors that disproportionately afflicts communities of color. Leveraging existing large-scale genome-wide association studies (GWAS), polygenic risk scores (PRS) have shown promise to complement established clinical risk factors and intervention paradigms, and improve early diagnosis and prevention of T2D. However, to date, T2D PRS have been most widely developed and validated in individuals of European descent. Comprehensive assessment of T2D PRS in non-European populations is critical for equitable deployment of PRS to clinical practice that benefits global populations.

METHODS:

We integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 cases; 9657 controls), and the Taiwan Biobank (4570 cases; 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts.

RESULTS:

The trans-ancestry PRS was significantly associated with T2D status across the ancestral groups examined. The top 2% of the PRS distribution can identify individuals with an approximately 2.5-4.5-fold of increase in T2D risk, which corresponds to the increased risk of T2D for first-degree relatives. The post hoc ancestry adjustment method eliminated major distributional differences in the PRS across ancestries without compromising its predictive performance.

CONCLUSIONS:

By integrating T2D GWAS from multiple populations, we developed and validated a trans-ancestry PRS, and demonstrated its potential as a meaningful index of risk among diverse patients in clinical settings. Our efforts represent the first step towards the implementation of the T2D PRS into routine healthcare.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 2 / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Diabetes Mellitus Tipo 2 / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article