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The Polygenic and Monogenic Basis of Blood Traits and Diseases.
Vuckovic, Dragana; Bao, Erik L; Akbari, Parsa; Lareau, Caleb A; Mousas, Abdou; Jiang, Tao; Chen, Ming-Huei; Raffield, Laura M; Tardaguila, Manuel; Huffman, Jennifer E; Ritchie, Scott C; Megy, Karyn; Ponstingl, Hannes; Penkett, Christopher J; Albers, Patrick K; Wigdor, Emilie M; Sakaue, Saori; Moscati, Arden; Manansala, Regina; Lo, Ken Sin; Qian, Huijun; 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, Kumaraswamy N; Wilson, Peter W F; Choquet, Hélène; Danesh, John; Di Angelantonio, Emanuele; Dimou, Niki; Ding, Jingzhong; Elliott, Paul; Esko, Tõnu; Evans, Michele K; Felix, Stephan B; Floyd, James S; Broer, Linda; Grarup, Niels; Guo, Michael H; Guo, Qi; Greinacher, Andreas; Haessler, Jeff; Hansen, Torben; Howson, Joanna M M; Huang, Wei.
Afiliación
  • Vuckovic D; Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK; National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambridge, CB1 8RN, 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 MIT and Harvard, Cambridge, MA, 02142, USA; Harvard-MIT Health Sciences and Technology, Harvard Medical S
  • Akbari P; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK; National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Donor Health and Genomics, University of Cambridge, Cambr
  • 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 MIT and Harvard, Cambridge, MA, 02142, USA.
  • Mousas A; Montreal Heart Institute, Montreal, Quebec, H1T 1C8, Canada.
  • Jiang T; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge
  • 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.
  • Tardaguila M; Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Huffman JE; Center for Population Genomics, Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, 02130, USA.
  • Ritchie SC; Department of Public Health and Primary Care, Cambridge Baker Systems Genomics Initiative, University of Cambridge, Cambridge, CB1 8RN, UK; Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, VIC 3004, Australia; Department of Public Health and Prima
  • Megy K; Department of Haematology, University of Cambridge, Cambridge, CB2 0PT, UK; National Institute for Health Research (NIHR) BioResource, Cambridge University Hospitals, Cambridge, CB2 0PT, UK; National Health Service (NHS) Blood and Transplant, Cambridge Biomedical Campus, Cambridge, CB2 0PT, UK.
  • Ponstingl H; Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Penkett CJ; National Institute for Health Research (NIHR) BioResource, Cambridge University Hospitals, Cambridge, CB2 0PT, UK; Department of Haematology, University of Cambridge, Cambridge, CB2 0PT, UK.
  • Albers PK; Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • Wigdor EM; Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, UK.
  • 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.
  • Moscati A; Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, 10029, USA.
  • Manansala R; Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, WI, 53201, USA.
  • Lo KS; Montreal Heart Institute, Montreal, Quebec, H1T 1C8, Canada.
  • Qian H; Department of Statistics and Operation Research, University of North Carolina, Chapel Hill, NC, 27599, USA.
  • 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 1QU, 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; Hasso-Plattner-Institut, Universität Potsdam, Potsdam, 14469, Germany; Icahn School of Medicine at Mount Sinai, The Charles Bronfman Institute for Personalized Medicine, New York, NY, 10029, USA.
  • 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 GE, the Netherlands.
  • Chitrala KN; Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD, 21224, USA.
  • Wilson PWF; Atlanta VA Medical Center, Decatur, GA, 30033, USA.
  • Choquet H; Division of Research, Kaiser Permanente Northern California, Oakland, CA, 94612, USA.
  • Danesh J; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, CB10 1SA, UK; National Institute for Health Rese
  • Di Angelantonio E; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, CB10 1SA, UK; National Institute for Health Rese
  • 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, W2 1NY, UK; Medical Research Council Centre for Environment and Health, Imperial College London,
  • Esko T; Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
  • Evans MK; Laboratory of Epidemiology and Population Science, National Institute on Aging/NIH, Baltimore, MD, 21224, USA.
  • Felix SB; Department of Internal Medicine B, University Medicine Greifswald, Greifswald, 17475, Germany; German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, 17475, Germany.
  • 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 GE, 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 MIT and Harvard, Cambridge, MA, 02142, USA; Department of Neurology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • Guo Q; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK.
  • 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, 98101, 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; Department of Public Health and Primary Care, British Heart Foundation Cardiovascular Epidemiology Unit, University of Cambridge, Cambridge, CB1 8RN, UK; National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge and Cambridge University Hospitals, Cambridge
  • 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.
Cell ; 182(5): 1214-1231.e11, 2020 09 03.
Article en En | MEDLINE | ID: mdl-32888494
ABSTRACT
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Herencia Multifactorial Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Herencia Multifactorial Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Female / Humans / Male Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Reino Unido