Journal article

Rare and low-frequency coding variants alter human adult height.

  • Marouli E William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Graff M Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Medina-Gomez C Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
  • Lo KS Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
  • Wood AR Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Kjaer TR Department of Molecular Biology and Genetics, Aarhus University, Aarhus, 8000, Denmark.
  • Fine RS Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Lu Y Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA.
  • Schurmann C The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Highland HM Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Rüeger S Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010, Switzerland.
  • Thorleifsson G deCODE Genetics/Amgen inc., Reykjavik, 101, Iceland.
  • Justice AE Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Lamparter D Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
  • Stirrups KE William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Turcot V Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
  • Young KL Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Winkler TW Department of Genetic Epidemiology, University of Regensburg, Regensburg, D-93051, Germany.
  • Esko T Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Karaderi T Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Locke AE Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Masca NG Department of Cardiovascular Sciences, Univeristy of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
  • Ng MC Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Mudgal P Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Rivas MA Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Vedantam S Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Mahajan A Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Guo X Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
  • Abecasis G Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Aben KK Netherlands Comprehensive Cancer Organisation, Utrecht, 3501 DB, The Netherlands.
  • Adair LS Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
  • Alam DS Centre for Control of Chronic Diseases (CCCD), Dhaka, 1212, Bangladesh.
  • Albrecht E Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  • Allin KH The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Allison M Department of Family Medicine &Public Health, University of California, San Diego, La Jolla, California 92093, USA.
  • Amouyel P INSERM U1167, Lille, F-59019, France.
  • Appel EV The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Arveiler D Department of Epidemiology and Public Health, University of Strasbourg, Strasbourg, F-67085, France.
  • Asselbergs FW Department of Cardiology, Division Heart &Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Auer PL Zilber School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, USA.
  • Balkau B INSERM U1018, Centre de recherche en Épidemiologie et Sante des Populations (CESP), Villejuif, France.
  • Banas B Department of Nephrology, University Hospital Regensburg, Regensburg, 93042, Germany.
  • Bang LE Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, 2100, Denmark.
  • Benn M Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2730, Denmark.
  • Bergmann S Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
  • Bielak LF Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Blüher M IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
  • Boeing H Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, 14558, Germany.
  • Boerwinkle E School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
  • Böger CA Department of Nephrology, University Hospital Regensburg, Regensburg, 93042, Germany.
  • Bonnycastle LL Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Bork-Jensen J The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Bots ML Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  • Bottinger EP The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
  • Bowden DW Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Brandslund I Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, 7100, Denmark.
  • Breen G MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London &NIHR Biomedical Research Centre for Mental Health at the Maudsley, London, SE5 8AF, UK.
  • Brilliant MH Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, USA.
  • Broer L Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
  • Burt AA Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
  • Butterworth AS MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Carey DJ The Sigfried and Janet Weis Center for Research, Danville, Pennsylvania 17822, USA.
  • Caulfield MJ William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Chambers JC Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex UB1 3HW, UK.
  • Chasman DI Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Chen YI Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
  • Chowdhury R MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Christensen C Medical Department, Lillebaelt Hospital, Vejle, 7100, Denmark.
  • Chu AY Division of Preventive Medicine, Brigham and Women's and Harvard Medical School, Boston, Massachusetts 02215, USA.
  • Cocca M Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, 34100, Italy.
  • Collins FS Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Cook JP Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
  • Corley J Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Galbany JC Department of Human Genetics, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Cox AJ Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Cuellar-Partida G Diamantina Institute, University of Qeensland, Brisbane, Queensland, 4072, Australia.
  • Danesh J MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Davies G Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • de Bakker PI Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
  • de Borst GJ Department of Vascular Surgery, Division of Surgical Specialties, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
  • de Denus S Montreal Heart Institute, Montreal, Quebec H1T 1C8, Canada.
  • de Groot MC Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, 3508 GA, The Netherlands.
  • de Mutsert R Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
  • Deary IJ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Dedoussis G Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece.
  • Demerath EW Division of Epidemiology &Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota 55454, USA.
  • den Hollander AI Department of Ophthalmology, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Dennis JG Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Di Angelantonio E MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Drenos F Institute of Cardiovascular Science, University College London, London WC1E 6JF, UK.
  • Du M Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, Washington 98109, USA.
  • Dunning AM Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
  • Easton DF Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Ebeling T Department of Medicine, Oulu University Hospital, Oulu, 90029, Finland.
  • Edwards TL Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee 37203, USA.
  • Ellinor PT Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Elliott P Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Evangelou E Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, UK.
  • Farmaki AE Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, 17671, Greece.
  • Faul JD Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, Michigan 48104, USA.
  • Feitosa MF Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, StLouis, Missouri 63108, USA.
  • Feng S Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Ferrannini E CNR Institute of Clinical Physiology, Pisa, Italy.
  • Ferrario MM Research Center on Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, 21100, Italy.
  • Ferrieres J Toulouse University School of Medicine, Toulouse, TSA 50032 31059, France.
  • Florez JC Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Ford I University of Glasgow, Glasgow G12 8QQ, UK.
  • Fornage M Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
  • Franks PW Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-20502, Sweden.
  • Frikke-Schmidt R Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Galesloot TE Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Gan W Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Gandin I Department of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
  • Gasparini P Department of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
  • Giedraitis V Geriatrics, Department of Public Health, Uppsala University, Uppsala, 751 85, Sweden.
  • Giri A Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee 37203, USA.
  • Girotto G Department of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
  • Gordon SD QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
  • Gordon-Larsen P Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Gorski M Department of Genetic Epidemiology, University of Regensburg, Regensburg, D-93051, Germany.
  • Grarup N The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Grove ML School of Public Health, Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
  • Gudnason V Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
  • Gustafsson S Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 751 41, Sweden.
  • Hansen T The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Harris KM Carolina Population Center, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Harris TB Laboratory of Epidemiology and Population Sciences, National Institute on Aging, Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892, USA.
  • Hattersley AT University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.
  • Hayward C MRCHGU, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • He L Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, North Carolina 27708, USA.
  • Heid IM Department of Genetic Epidemiology, University of Regensburg, Regensburg, D-93051, Germany.
  • Heikkilä K Department of Public Health, University of Helsinki, Helsinki, FI-00014, Finland.
  • Helgeland Ø Department of Pediatrics, Haukeland University Hospital, Bergen, 5021, Norway.
  • Hernesniemi J Department of Cardiology, Heart Center, Tampere University Hospital, Tampere, 33521, Finland.
  • Hewitt AW Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, 3002, Australia.
  • Hocking LJ Generation Scotland, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Hollensted M The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Holmen OL K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, NTNU, Norwegian University of Science and Technology, Trondheim, 7600, Norway.
  • Hovingh GK AMC, Department of Vascular Medicine, Amsterdam, 1105 AZ, The Netherlands.
  • Howson JM MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
  • Hoyng CB Department of Ophthalmology, Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Huang PL Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Hveem K HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, 7600, Norway.
  • Ikram MA Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE, The Netherlands.
  • Ingelsson E Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, 751 41, Sweden.
  • Jackson AU Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Jansson JH Department of Public Health &Clinical Medicine, Umeå University, Umeå, SE-90185, Sweden.
  • Jarvik GP Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
  • Jensen GB The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, 2000, Denmark.
  • Jhun MA Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Jia Y Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
  • Jiang X Department of Preventive Medicine, Keck School of Medicine of the University of California, Los Angeles, California 90089, USA.
  • Johansson S KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, 5020, Norway.
  • Jørgensen ME National Institute of Public Health, University of Southern Denmark, Copenhagen, 1353, Denmark.
  • Jørgensen T Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Jousilahti P National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
  • Jukema JW Department of Cardiology, Leiden University Medical Center, Leiden, 2333, The Netherlands.
  • Kahali B Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Kahn RS Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
  • Kähönen M Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, 33014, Finland.
  • Kamstrup PR Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2730, Denmark.
  • Kanoni S William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Kaprio J Department of Public Health, University of Helsinki, Helsinki, FI-00014, Finland.
  • Karaleftheri M Echinos Medical Centre, Echinos, Greece.
  • Kardia SL Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
  • Karpe F Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
  • Kee F UKCRC Centre of Excellence for Public Health Research, Queens University Belfast, Belfast BT12 6BJ, UK.
  • Keeman R Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam, 1066 CX, The Netherlands.
  • Kiemeney LA Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Kitajima H Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Kluivers KB Radboud University Medical Center, Nijmegen, 6500 HB, The Netherlands.
  • Kocher T Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald, Greifswald, 17475, Germany.
  • Komulainen P Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
  • Kontto J National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
  • Kooner JS Department of Cardiology, London North West Healthcare NHS Trust, Ealing Hospital, Middlesex UB1 3HW, UK.
  • Kooperberg C Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
  • Kovacs P IFB Adiposity Diseases, University of Leipzig, Leipzig, 04103, Germany.
  • Kriebel J German Center for Diabetes Research, München-Neuherberg, 85764, Germany.
  • Kuivaniemi H The Sigfried and Janet Weis Center for Research, Danville, Pennsylvania 17822, USA.
  • Küry S CHU Nantes, Service de Génétique Médicale, Nantes, 44093, France.
  • Kuusisto J Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland.
  • La Bianca M Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, 34137, Italy.
  • Laakso M Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland.
  • Lakka TA Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
  • Lange EM Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Lange LA Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Langefeld CD Department of Biostatistical Sciences and Center for Public Health Genomics, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Langenberg C MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Larson EB Department of Medicine, University of Washington, Seattle, Washington 98195, USA.
  • Lee IT Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan.
  • Lehtimäki T Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
  • Lewis CE Division of Preventive Medicine University of Alabama at Birmingham, Birmingham, Alabama 35205, USA.
  • Li H Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China, Shanghai, 200031, China.
  • Li J Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA.
  • Li-Gao R Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
  • Lin H Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
  • Lin LA Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
  • Lin X Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai, People's Republic of China, Shanghai, 200031, China.
  • Lind L Uppsala University, Uppsala, 75185, Sweden.
  • Lindström J National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
  • Linneberg A Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2200, Denmark.
  • Liu Y Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical Center, Torrance, California 90502, USA.
  • Liu Y Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
  • Lophatananon A Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK.
  • Luan J MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Lubitz SA Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Lyytikäinen LP Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
  • Mackey DA Centre for Ophthalmology and Vision Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, 6009, Australia.
  • Madden PA Department of Psychiatry, Washington University, Saint Louis, Missouri 63110, USA.
  • Manning AK Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Männistö S National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
  • Marenne G Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
  • Marten J MRCHGU, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK.
  • Martin NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.
  • Mazul AL Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Meidtner K German Center for Diabetes Research, München-Neuherberg, 85764, Germany.
  • Metspalu A Estonian Genome Center, University of Tartu, Tartu, 51010, Estonia.
  • Mitchell P Westmead Millennium Institute of Medical Research, Centre for Vision Research and Department of Ophthalmology, University of Sydney, Sydney, New South Wales, 2022, Australia.
  • Mohlke KL Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
  • Mook-Kanamori DO Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2300 RC, The Netherlands.
  • Morgan A Department of Medical Sciences, University of Trieste, Trieste, 34137, Italy.
  • Morris AD Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK.
  • Morris AP Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • Müller-Nurasyid M Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, D-85764, Germany.
  • Munroe PB William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Nalls MA Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland 20892, USA.
  • Nauck M DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Greifswald, 17475, Germany.
  • Nelson CP Department of Cardiovascular Sciences, Univeristy of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
  • Neville M Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
  • Nielsen SF Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2730, Denmark.
  • Nikus K Department of Cardiology, Heart Center, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, 33521, Finland.
  • Njølstad PR Department of Pediatrics, Haukeland University Hospital, Bergen, 5021, Norway.
  • Nordestgaard BG Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2730, Denmark.
  • Ntalla I William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • O'Connel JR Program in Personalized Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
  • Oksa H Department of Medicine, Tampere University Hospital, Tampere, 33521, Finland.
  • Loohuis LM Center for Neurobehavioral Genetics, UCLA, Los Angeles, California 90095, USA.
  • Ophoff RA Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
  • Owen KR Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
  • Packard CJ University of Glasgow, Glasgow G12 8QQ, UK.
  • Padmanabhan S University of Glasgow, Glasgow G12 8QQ, UK.
  • Palmer CN Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
  • Pasterkamp G Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands.
  • Patel AP Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
  • Pattie A Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK.
  • Pedersen O The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark.
  • Peissig PL Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, USA.
  • Peloso GM Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  • Pennell CE School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, 6009, Australia.
  • Perola M National Institute for Health and Welfare, Helsinki, FI-00271, Finland.
  • Perry JA Program in Personalized Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
  • Perry JR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Person TN Marshfield Clinic Research Foundation, Marshfield, Wisconsin 54449, USA.
  • Pirie A Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
  • Polasek O Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh EH8 9AG, UK.
  • Posthuma D Center for Neurogenomics and Cognitive Research, Department Complex Trait Genetics, VU University, Amsterdam, 1081 HV, The Netherlands.
  • Raitakari OT Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, 20521, Finland.
  • Rasheed A Centre for Non-Communicable Diseases, Karachi, Pakistan.
  • Rauramaa R Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
  • Reilly DF MRL, Merck &Co., Inc., Genetics and Pharmacogenomics, Boston, Massachusetts 02115, USA.
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  • Lettre G
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  • 2017-02-02
Published in:
  • Nature. - 2017
English Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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