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Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations.
Chen, Ming-Huei; Raffield, Laura M; Mousas, Abdou; Sakaue, Saori; Huffman, Jennifer E; Moscati, Arden; Trivedi, Bhavi; Jiang, Tao; Akbari, Parsa; Vuckovic, Dragana; Bao, Erik L; Zhong, Xue; Manansala, Regina; Laplante, Véronique; Chen, Minhui; Lo, Ken Sin; Qian, Huijun; Lareau, Caleb A; Beaudoin, Mélissa; Hunt, Karen A; Akiyama, Masato; Bartz, Traci M; Ben-Shlomo, Yoav; Beswick, Andrew; Bork-Jensen, Jette; Bottinger, Erwin P; Brody, Jennifer A; van Rooij, Frank J A; Chitrala, Kumaraswamynaidu; Cho, Kelly; Choquet, Hélène; Correa, Adolfo; Danesh, John; Di Angelantonio, Emanuele; Dimou, Niki; Ding, Jingzhong; Elliott, Paul; Esko, Tõnu; Evans, Michele K; Floyd, James S; Broer, Linda; Grarup, Niels; Guo, Michael H; Greinacher, Andreas; Haessler, Jeff; Hansen, Torben; Howson, Joanna M M; Huang, Qin Qin; Huang, Wei; Jorgenson, Eric.
Afiliação
  • Chen MH; The Framingham Heart Study, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA 01702, USA.
  • Raffield LM; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Mousas A; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Sakaue S; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan.
  • Huffman JE; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  • Moscati A; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Trivedi B; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
  • Jiang T; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Akbari P; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; MRC Biostatistics Unit, University of Cambridge, Cambridge CB2 0SR, UK; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; The National Institute for Heal
  • Vuckovic D; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
  • Bao EL; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA.
  • Zhong X; Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
  • Manansala R; Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI 53201, USA.
  • Laplante V; Département de Pharmacologie et Physiologie, Faculty of Medicine, Université de Montréal, Montreal, QC H3T 1J4, Canada.
  • Chen M; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
  • Lo KS; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Qian H; Department of Statistics and Operation Research, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Lareau CA; Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA.
  • Beaudoin M; Montreal Heart Institute, Montreal, QC H1T 1C8, Canada.
  • Hunt KA; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
  • Akiyama M; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan; Department of Ocular Pathology and Imaging Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8581, Japan.
  • Bartz TM; Department of Biostatistics, University of Washington, Seattle, WA 98101, USA.
  • Ben-Shlomo Y; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK.
  • Beswick A; Translational Health Sciences, Musculoskeletal Research Unit, Bristol Medical School, University of Bristol, Bristol BS10 5NB, UK.
  • Bork-Jensen J; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Bottinger EP; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Hasso-Plattner-Institut, Universität Potsdam, Potsdam 14469, Germany.
  • Brody JA; Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • van Rooij FJA; Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam 3015, the Netherlands.
  • Chitrala K; Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD 21224, USA.
  • Cho K; Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA; Department of Medicine, Division on Aging, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Choquet H; Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
  • Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA.
  • Danesh J; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Ge
  • Di Angelantonio E; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge CB2 0QQ, UK; Health Da
  • Dimou N; Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon 69008, France; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina 45110, Greece.
  • Ding J; Department of Internal Medicine, Section of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA.
  • Elliott P; Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK; Imperial Biomedical Research Centre, Imperial College London and Imperial College NHS Healthcare Trust, London SW7 2AZ, UK; Medical Research Council-Public Health England Centre for Environment, Imperial Colleg
  • Esko T; Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA.
  • Evans MK; Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD 21224, USA.
  • Floyd JS; Department of Medicine, University of Washington, Seattle, WA 98101, USA; Department of Epidemiology, University of Washington, Seattle, WA 98101, USA.
  • Broer L; Department of Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015, the Netherlands.
  • Grarup N; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Guo MH; Broad Institute of Harvard and MIT, Cambridge, MA 02446, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Greinacher A; Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald 17475, Germany.
  • Haessler J; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  • Howson JMM; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; Novo Nordisk Research Centre Oxford, Innovation Building, Old Road Campus, Oxford OX3 7FZ, UK.
  • Huang QQ; Human Genetics, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.
  • Huang W; Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai 201203, China.
  • Jorgenson E; Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA.
Cell ; 182(5): 1198-1213.e14, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32888493
Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mutação de Sentido Incorreto / Polimorfismo de Nucleotídeo Único / Povo Asiático / População Branca Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Mutação de Sentido Incorreto / Polimorfismo de Nucleotídeo Único / Povo Asiático / População Branca Idioma: En Ano de publicação: 2020 Tipo de documento: Article