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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.
Li, Chen; Stoma, Svetlana; Lotta, Luca A; Warner, Sophie; Albrecht, Eva; Allione, Alessandra; Arp, Pascal P; Broer, Linda; Buxton, Jessica L; Da Silva Couto Alves, Alexessander; Deelen, Joris; Fedko, Iryna O; Gordon, Scott D; Jiang, Tao; Karlsson, Robert; Kerrison, Nicola; Loe, Taylor K; Mangino, Massimo; Milaneschi, Yuri; Miraglio, Benjamin; Pervjakova, Natalia; Russo, Alessia; Surakka, Ida; van der Spek, Ashley; Verhoeven, Josine E; Amin, Najaf; Beekman, Marian; Blakemore, Alexandra I; Canzian, Federico; Hamby, Stephen E; Hottenga, Jouke-Jan; Jones, Peter D; Jousilahti, Pekka; Mägi, Reedik; Medland, Sarah E; Montgomery, Grant W; Nyholt, Dale R; Perola, Markus; Pietiläinen, Kirsi H; Salomaa, Veikko; Sillanpää, Elina; Suchiman, H Eka; van Heemst, Diana; Willemsen, Gonneke; Agudo, Antonio; Boeing, Heiner; Boomsma, Dorret I; Chirlaque, Maria-Dolores; Fagherazzi, Guy; Ferrari, Pietro.
Afiliação
  • Li C; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom.
  • Stoma S; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom.
  • Lotta LA; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom.
  • Warner S; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom.
  • Albrecht E; Institute of Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, D-85764 Neuherberg, Germany.
  • Allione A; Department of Medical Science, Genomic Variation and Translational Research Unit, University of Turin, 10126 Turin, Italy; Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
  • Arp PP; Department of Internal Medicine, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands.
  • Broer L; Department of Internal Medicine, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands.
  • Buxton JL; School of Life Sciences, Pharmacy, and Chemistry, Kingston University, Kingston upon Thames, KT1 2EE, United Kingdom; Genetics and Genomic Medicine Programme, UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, United Kingdom.
  • Da Silva Couto Alves A; School of Public Health, Imperial College London, St Mary's Hospital, London W2 1PG, United Kingdom; School of Biosciences and Medicine, University of Surrey, Guildford, GU2 7XH, United Kingdom.
  • Deelen J; Max Planck Institute for Biology of Ageing, D-50931, Cologne, Germany; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands.
  • Fedko IO; Department of Biological Psychology, Vrije Universteit, 1081 BT Amsterdam, the Netherlands.
  • Gordon SD; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Queensland, 4006 Australia.
  • Jiang T; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom.
  • Karlsson R; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden.
  • Kerrison N; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom.
  • Loe TK; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Mangino M; Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom; NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London SE1 9RT, United Kingdom.
  • Milaneschi Y; Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije Universiteit, 1081HJ, Amsterdam, the Netherlands.
  • Miraglio B; Institute for Molecular Medicine Finland (FIMM), PO Box 20, 00014 University of Helsinki, Finland.
  • Pervjakova N; Estonian Genome Centre, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia.
  • Russo A; Department of Medical Science, Genomic Variation and Translational Research Unit, University of Turin, 10126 Turin, Italy; Italian Institute for Genomic Medicine (IIGM), 10126 Turin, Italy.
  • Surakka I; Institute for Molecular Medicine Finland (FIMM), PO Box 20, 00014 University of Helsinki, Finland; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  • van der Spek A; Department of Epidemiology, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands.
  • Verhoeven JE; Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije Universiteit, 1081HJ, Amsterdam, the Netherlands.
  • Amin N; Department of Epidemiology, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands.
  • Beekman M; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands.
  • Blakemore AI; Department of Life Sciences, Brunel University London, Uxbridge UB8 3PH, United Kingdom; Department of Medicine, Imperial College London, London, W12 0HS, United Kingdom.
  • Canzian F; Genomic Epidemiology Group, German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
  • Hamby SE; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom.
  • Hottenga JJ; Department of Biological Psychology, Vrije Universteit, 1081 BT Amsterdam, the Netherlands.
  • Jones PD; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom.
  • Jousilahti P; Department of Public Health Solutions, Finnish Institute for Health and Welfare, PO Box 30, FI-00271 Helsinki, Finland.
  • Mägi R; Estonian Genome Centre, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia.
  • Medland SE; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Queensland, 4006 Australia.
  • Montgomery GW; Institute for Molecular Bioscience, The University of Queensland, 4072, Queensland, Australia.
  • Nyholt DR; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Queensland, 4006 Australia; School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, 4059, Australia.
  • Perola M; Department of Public Health Solutions, Finnish Institute for Health and Welfare, PO Box 30, FI-00271 Helsinki, Finland; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, Biomedicum 1, PO Box 63, 00014 University of Helsinki, Finland.
  • Pietiläinen KH; Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Haartmaninkatu 8, 00014 University of Helsinki, Helsinki, Finland; Obesity Center, Abdominal Center, Endocrinology, Helsinki University Hospital and University of Helsinki, Haartmaninkatu 4, 00029 HUS, Helsinki, Finland.
  • Salomaa V; Department of Public Health Solutions, Finnish Institute for Health and Welfare, PO Box 30, FI-00271 Helsinki, Finland.
  • Sillanpää E; Institute for Molecular Medicine Finland (FIMM), PO Box 20, 00014 University of Helsinki, Finland; Gerontology Research Center, Faculty of Sport and Health Sciences, PO Box 35, 40014 University of Jyväskylä, Finland.
  • Suchiman HE; Department of Biomedical Data Sciences, Section of Molecular Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands.
  • van Heemst D; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, the Netherlands.
  • Willemsen G; Department of Biological Psychology, Vrije Universteit, 1081 BT Amsterdam, the Netherlands.
  • Agudo A; Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-ICO, Group of Research on Nutrition and Cancer, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet of Llobregat, 08908 Barcelona, Spain.
  • Boeing H; German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
  • Boomsma DI; Department of Biological Psychology, Vrije Universteit, 1081 BT Amsterdam, the Netherlands.
  • Chirlaque MD; Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008, Murcia, Spain; CIBER of Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain.
  • Fagherazzi G; Center of Research in Epidemiology and Population Health, UMR 1018 Inserm, Institut Gustave Roussy, Paris-Sud Paris-Saclay University, 94805 Villejuif, France; Digital Epidemiology Research Hub, Department of Population Health, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg.
  • Ferrari P; International Agency for Research on Cancer, 69372 Lyon, France.
Am J Hum Genet ; 106(3): 389-404, 2020 03 05.
Article em En | MEDLINE | ID: mdl-32109421
ABSTRACT
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Telômero / Estudo de Associação Genômica Ampla / Leucócitos / Nucleotídeos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Am J Hum Genet Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Telômero / Estudo de Associação Genômica Ampla / Leucócitos / Nucleotídeos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Am J Hum Genet Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Reino Unido