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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.
Mahajan, Anubha; Spracklen, Cassandra N; Zhang, Weihua; Ng, Maggie C Y; Petty, Lauren E; Kitajima, Hidetoshi; Yu, Grace Z; Rüeger, Sina; Speidel, Leo; Kim, Young Jin; Horikoshi, Momoko; Mercader, Josep M; Taliun, Daniel; Moon, Sanghoon; Kwak, Soo-Heon; Robertson, Neil R; Rayner, Nigel W; Loh, Marie; Kim, Bong-Jo; Chiou, Joshua; Miguel-Escalada, Irene; Della Briotta Parolo, Pietro; Lin, Kuang; Bragg, Fiona; Preuss, Michael H; Takeuchi, Fumihiko; Nano, Jana; Guo, Xiuqing; Lamri, Amel; Nakatochi, Masahiro; Scott, Robert A; Lee, Jung-Jin; Huerta-Chagoya, Alicia; Graff, Mariaelisa; Chai, Jin-Fang; Parra, Esteban J; Yao, Jie; Bielak, Lawrence F; Tabara, Yasuharu; Hai, Yang; Steinthorsdottir, Valgerdur; Cook, James P; Kals, Mart; Grarup, Niels; Schmidt, Ellen M; Pan, Ian; Sofer, Tamar; Wuttke, Matthias; Sarnowski, Chloe; Gieger, Christian.
Afiliación
  • Mahajan A; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. mahajan.anubha@gene.com.
  • Spracklen CN; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. mahajan.anubha@gene.com.
  • Zhang W; Genentech, South San Francisco, CA, USA. mahajan.anubha@gene.com.
  • Ng MCY; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Petty LE; Department of Epidemiology and Biostatistics, University of Massachusetts Amherst, Amherst, MA, USA.
  • Kitajima H; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Yu GZ; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, UK.
  • Rüeger S; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Speidel L; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Kim YJ; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
  • Horikoshi M; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Mercader JM; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Taliun D; The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, Sendai, Japan.
  • Moon S; Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
  • Kwak SH; Cancer Center, Tohoku University Hospital, Tohoku University, Sendai, Japan.
  • Robertson NR; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Rayner NW; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Loh M; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Kim BJ; Genetics Institute, University College London, London, UK.
  • Chiou J; Francis Crick Institute, London, UK.
  • Miguel-Escalada I; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, Republic of Korea.
  • Della Briotta Parolo P; Laboratory for Genomics of Diabetes and Metabolism, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Lin K; Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Bragg F; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Preuss MH; Harvard Medical School, Boston, MA, USA.
  • Takeuchi F; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Nano J; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Guo X; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, Republic of Korea.
  • Lamri A; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Nakatochi M; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
  • Scott RA; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Lee JJ; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Huerta-Chagoya A; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Graff M; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chai JF; Department of Human Genetics, Wellcome Sanger Institute, Hinxton, UK.
  • Parra EJ; Institute of Translational Genomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Yao J; Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
  • Bielak LF; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • Tabara Y; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR) and National University of Singapore (NUS), Singapore, Singapore.
  • Hai Y; Division of Genome Science, Department of Precision Medicine, National Institute of Health, Cheongju-si, Republic of Korea.
  • Steinthorsdottir V; Biomedical Sciences Graduate Studies Program, University of California San Diego, La Jolla, CA, USA.
  • Cook JP; Internal Medicine Research Unit, Pfizer Worldwide Research, Cambridge, MA, USA.
  • Kals M; Regulatory Genomics and Diabetes, Centre for Genomic Regulation, the Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Grarup N; Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM), Madrid, Spain.
  • Schmidt EM; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Pan I; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Sofer T; Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Wuttke M; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK.
  • Sarnowski C; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Gieger C; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
Nat Genet ; 54(5): 560-572, 2022 05.
Article en En | MEDLINE | ID: mdl-35551307
ABSTRACT
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Tipo 2 / Estudio de Asociación del Genoma Completo Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article