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Journal article

Disentangling the genetics of lean mass.

  • Karasik D Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
  • Zillikens MC Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Hsu YH Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
  • Aghdassi A Department of Medicine A, University of Greifswald, Greifswald, Germany.
  • Akesson K Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
  • Amin N Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Barroso I Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
  • Bennett DA Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
  • Bertram L Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
  • Bochud M University Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Borecki IB Division of Statistical Genomics, Department of Genetics.
  • Broer L Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Buchman AS Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
  • Byberg L Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Campbell H Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom.
  • Campos-Obando N Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Cauley JA Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
  • Cawthon PM California Pacific Medical Center Research Institute, San Francisco, CA.
  • Chambers JC Cardiology, Ealing Hospital NHS Trust, London, United Kingdom.
  • Chen Z Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
  • Cho NH Department of Preventive Medicine, Ajou University School of Medicine, Youngtong-Gu, Suwon, Korea.
  • Choi HJ Department of Internal Medicine.
  • Chou WC Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
  • Cummings SR California Pacific Medical Center Research Institute, San Francisco, CA.
  • de Groot LCPGM Division of Human Nutrition, Wageningen University, AFSG, Wageningen, The Netherlands.
  • De Jager PL Center for Translational and Computational Neuroimmunology, Neurology, Columbia University Medical Center, New York, NY.
  • Demuth I Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Diatchenko L Regional Center for Neurosensory Disorders, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Econs MJ Department of Medicine and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
  • Eiriksdottir G Icelandic Heart Association Holtasmari, Kopavogur, Iceland.
  • Enneman AW Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Eriksson J Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Eriksson JG National Institute for Health and Welfare, Helsinki, Finland.
  • Estrada K Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Evans DS California Pacific Medical Center Research Institute, San Francisco, CA.
  • Feitosa MF Division of Statistical Genomics, Department of Genetics.
  • Fu M Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
  • Gieger C Research Unit of Molecular Epidemiology.
  • Grallert H Research Unit of Molecular Epidemiology.
  • Gudnason V Icelandic Heart Association Holtasmari, Kopavogur, Iceland.
  • Lenore LJ Laboratory of Epidemiology and Population Sciences, Intramural Research Program, NIA, Bethesda, MD.
  • Hayward C MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, United Kingdom.
  • Hofman A Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Homuth G Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
  • Huffman KM Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC.
  • Husted LB Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark.
  • Illig T Research Unit of Molecular Epidemiology.
  • Ingelsson E Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA.
  • Ittermann T Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
  • Jansson JO Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Johnson T University Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Biffar R Centre of Oral Health, Department of Prosthetic Dentistry, Gerodontology and Biomaterials, University of Greifswald, Greifswald, Germany.
  • Jordan JM Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Jula A National Institute for Health and Welfare, Helsinki, Finland.
  • Karlsson M Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
  • Khaw KT Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
  • Kilpeläinen TO MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
  • Klopp N Research Unit of Molecular Epidemiology.
  • Kloth JSL Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Koller DL Department of Medicine and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
  • Kooner JS Cardiology, Ealing Hospital NHS Trust, London, United Kingdom.
  • Kraus WE Duke Molecular Physiology Institute and Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC.
  • Kritchevsky S Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
  • Kutalik Z University Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • Kuulasmaa T Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
  • Kuusisto J Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
  • Laakso M Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
  • Lahti J Helsinki Collegium Advanced Studies, University of Helsinki, Helsinki, Finland.
  • Lang T Department of Radiology and Biomedical Imaging, and School of Dentistry, UC San Francisco, San Francisco, CA.
  • Langdahl BL Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark.
  • Lerch MM Department of Medicine A, University of Greifswald, Greifswald, Germany.
  • Lewis JR School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
  • Lill C Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
  • Lind L Department. of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Lindgren C Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
  • Liu Y Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
  • Livshits G Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Ljunggren Ö Department. of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Loos RJF Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Lorentzon M Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Luan J Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Luben RN Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Malkin I Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • McGuigan FE Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
  • Medina-Gomez C Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Meitinger T Institute of Human Genetics, MRI, Technische Universität München, Munich, Germany.
  • Melhus H Department. of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Mellström D Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Michaëlsson K Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
  • Mitchell BD Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
  • Morris AP Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
  • Mosekilde L Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark.
  • Nethander M Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Newman AB Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
  • O'Connell JR Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
  • Oostra BA Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
  • Orwoll ES Oregon Health & Science University, Portland, OR.
  • Palotie A Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Peacock M Department of Medicine and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
  • Perola M National Institute for Health and Welfare, Helsinki, Finland.
  • Peters A Research Unit of Molecular Epidemiology.
  • Prince RL School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
  • Psaty BM Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA.
  • Räikkönen K Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
  • Ralston SH Molecular Medicine Centre, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom.
  • Ripatti S Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
  • Rivadeneira F Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Robbins JA Department of Medicine, University California at Davis, Sacramento, CA.
  • Rotter JI Institute for Translational Genomic and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor UCLA Medical Center, Torrance, CA.
  • Rudan I Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
  • Salomaa V National Institute for Health and Welfare, Helsinki, Finland.
  • Satterfield S Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
  • Schipf S Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
  • Shin CS Department of Internal Medicine.
  • Smith AV Icelandic Heart Association Holtasmari, Kopavogur, Iceland.
  • Smith SB Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC.
  • Soranzo N Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
  • Spector TD Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Campus, London, United Kingdom.
  • Stancáková A Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
  • Stefansson K University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
  • Steinhagen-Thiessen E Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Stolk L Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Streeten EA Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
  • Styrkarsdottir U deCODE Genetics, Reykjavik, Iceland.
  • Swart KMA Department of Epidemiology and Biostatistics, and the EMGO+ Institute; VU University Medical Center, Amsterdam, The Netherlands.
  • Thompson P Department of Pathology, Stony Brook University, Stony Brook, NY.
  • Thomson CA Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
  • Thorleifsson G deCODE Genetics, Reykjavik, Iceland.
  • Thorsteinsdottir U University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
  • Tikkanen E National Institute for Health and Welfare, Helsinki, Finland.
  • Tranah GJ California Pacific Medical Center Research Institute, San Francisco, CA.
  • Uitterlinden AG Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • van Duijn CM Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • van Schoor NM Department of Epidemiology and Biostatistics, and the EMGO+ Institute; VU University Medical Center, Amsterdam, The Netherlands.
  • Vandenput L Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Vollenweider P Department of Medicine, Internal Medicine, Lausanne University Hospital and Faculty of Biology and Medicine, Lausanne, Switzerland.
  • Völzke H Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
  • Wactawski-Wende J Department of Epidemiology and Environmental Health, University at Buffalo, SUNY, Buffalo, NY.
  • Walker M Institute of Cellular Medicine (Diabetes), The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
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  • Waterworth D Genetics, GlaxoSmithKline, King of Prussia, PA.
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  • Wichmann HE Institute of Epidemiology II.
  • Widen E Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
  • Williams FMK Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Campus, London, United Kingdom.
  • Wilson JF Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom.
  • Wright NC Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
  • Yerges-Armstrong LM Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
  • Yu L Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
  • Zhang W Cardiology, Ealing Hospital NHS Trust, London, United Kingdom.
  • Zhao JH MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
  • Zhou Y Department of Biostatistics, Boston University School of Public Health, Boston, MA.
  • Nielson CM Oregon Health & Science University, Portland, OR.
  • Harris TB Laboratory of Epidemiology and Population Sciences, Intramural Research Program, NIA, Bethesda, MD.
  • Demissie S Department of Biostatistics, Boston University School of Public Health, Boston, MA.
  • Kiel DP Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
  • Ohlsson C Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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  • 2019-02-06
Published in:
  • The American journal of clinical nutrition. - 2019
English Background
Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass.


Objectives
To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.


Methods
We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms).


Results
Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection.


Conclusions
In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/149278
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