Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.

Autor:	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., Franks P; Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502 Malmö, Sweden; Department of Public Health and Clinical Medicine, Umeå University, 90187 Umeå, Sweden., Gieger C; Institute of Epidemiology, Helmholtz Zentrum München-German Research Centre for Environmental Health, D-85764 Neuherberg, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D 85764 Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), D-85764 Neuherberg, Germany., Eriksson JG; Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014 University of Helsinki, Finland; Folkhälsan Research Centre, PO Box 20, 00014 University of Helsinki, Finland; Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597., Gunter M; International Agency for Research on Cancer, 69372 Lyon, France., Hägg S; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden., Hovatta I; SleepWell Research Program, Haartmaninkatu 3, 00014 University of Helsinki, Finland; Department of Psychology and Logopedics, Haartmaninkatu 3, 00014 University of Helsinki, Finland., Imaz L; Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, 20013 Donostia-San Sebastian, Spain; Biodonostia Health Research Institute, 20014 Donostia-San Sebastian, Spain., Kaprio J; Institute for Molecular Medicine Finland (FIMM), PO Box 20, 00014 University of Helsinki, Finland; Department of Public Health, PO Box 20, 00014 University of Helsinki, Finland., Kaaks R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Key T; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, OX3 7LF, United Kingdom., Krogh V; Epidemiology and Prevention Unit, Fondazione IRCCS-Istituto Nazionale dei Tumori, 20133 Milan, Italy., Martin NG; Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Queensland, 4006 Australia., Melander O; Department of Clinical Sciences, Hypertension, and Cardiovascular Disease, Lund University, 21428 Malmö, Sweden., Metspalu A; Estonian Genome Centre, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia., Moreno C; Instituto de Salud Pública, 31003 Pamplona, Spain., Onland-Moret NC; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, the Netherlands., Nilsson P; Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502 Malmö, Sweden., Ong KK; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom; Department of Paediatrics, University of Cambridge, CB2 0QQ, United Kingdom., Overvad K; Department of Public Health, Aarhus University, DK-8000 Aarhus, Denmark; Department of Cardiology, Aalborg University Hospital, DK-9000 Aalborg, Denmark., Palli D; Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research-ISPRO, 50139 Florence, Italy., Panico S; Dipartimento di Medicina Clinica e Chirurgia, Federico II University, 80131 Naples, Italy., Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17177, Sweden., Penninx BWJH; Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Amsterdam UMC/Vrije Universiteit, 1081HJ, Amsterdam, the Netherlands., Quirós JR; Consejería de Sanidad, Public Health Directorate, 33006 Asturias, Spain., Jarvelin MR; School of Public Health, Imperial College London, St Mary's Hospital, London W2 1PG, United Kingdom; School of Epidemiology and Biostatistics, Imperial College London, SW7 2AZ, United Kingdom., Rodríguez-Barranco M; Center of Research in Epidemiology and Population Health, UMR 1018 Inserm, Institut Gustave Roussy, Paris-Sud Paris-Saclay University, 94805 Villejuif, France; Andalusian School of Public Health (EASP), 18080 Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain., Scott RA; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom., Severi G; CESP, Facultés de médecine, Université Paris, 94805 Villejuif, France; Gustave Roussy, 94805 Villejuif, France; Department of Statistics, Computer Science, Applications 'G. Parenti,' University of Florence, 50134 Firenze, Italy., Slagboom PE; 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., Spector TD; Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, United Kingdom., Tjonneland A; Danish Cancer Society Research Center, 2100 Copenhagen, Denmark., Trichopoulou A; Hellenic Health Foundation, 11527 Athens, Greece., Tumino R; Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), 97100 Ragusa, Italy; Hyblean Association for Research on Epidemiology, No Profit Organization, 97100 Ragusa, Italy., Uitterlinden AG; Department of Internal Medicine, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands., van der Schouw YT; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CG Utrecht, the Netherlands., van Duijn CM; Department of Epidemiology, Erasmus Medical Centre, Postbus 2040, 3000 CA, Rotterdam, the Netherlands; Nuffield Department of Population Health, University of Oxford, OX3 7LF, United Kingdom., Weiderpass E; International Agency for Research on Cancer, 69372 Lyon, France., Denchi EL; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA; Laboratory of Chromosome Instability, National Cancer Institute, NIH, Bethesda, MD 20892 USA., Matullo G; 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., Butterworth AS; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, CB10 1SA, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom; BHF Cambridge Centre of Excellence, School of Clinical Medicine, Addenbrookes' Hospital, Cambridge, CB2 0QQ, United Kingdom; NIHR Cambridge Biomedical Research Centre, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom., Danesh J; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom; Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, CB10 1SA, United Kingdom; NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom; Department of Human Genetics, Wellcome Sanger Institute, Hinxton, CB10 1SA, United Kingdom; BHF Cambridge Centre of Excellence, School of Clinical Medicine, Addenbrookes' Hospital, Cambridge, CB2 0QQ, United Kingdom; NIHR Cambridge Biomedical Research Centre, School of Clinical Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom., Samani NJ; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom., Wareham NJ; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom., Nelson CP; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom., Langenberg C; MRC Epidemiology Unit, University of Cambridge, CB2 0SL, United Kingdom. Electronic address: Claudia.Langenberg@mrc-epid.cam.ac.uk., Codd V; Department of Cardiovascular Sciences, University of Leicester, LE3 9QP, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom. Electronic address: vc15@leicester.ac.uk.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2020 Mar 05; Vol. 106 (3), pp. 389-404. Date of Electronic Publication: 2020 Feb 27.
DOI:	10.1016/j.ajhg.2020.02.006
Abstrakt:	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. (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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