Disentangling the genetics of lean mass

David Karasik^{1

2}, M Carola Zillikens^{3

4}, Yi-Hsiang Hsu^{1

5

6}, Ali Aghdassi⁷, Kristina Akesson^{8

9}, Najaf Amin¹⁰, Inês Barroso^{11

12

13}, David A Bennett¹⁴, Lars Bertram¹⁵, Murielle Bochud¹⁶, Ingrid B Borecki^{17

18}, Linda Broer^{3

10}, Aron S Buchman¹⁴, Liisa Byberg¹⁹, Harry Campbell²⁰, Natalia Campos-Obando³, Jane A Cauley²¹, Peggy M Cawthon²², John C Chambers^{23

24

25

26}, Zhao Chen²⁷, Nam H Cho²⁸, Hyung Jin Choi^{29

30

31}, Wen-Chi Chou^{1

32}, Steven R Cummings²², Lisette C P G M de Groot³³, Phillip L De Jager^{34

35}, Ilja Demuth^{36

37}, Luda Diatchenko^{38

39}, Michael J Econs⁴⁰, Gudny Eiriksdottir⁴¹, Anke W Enneman³, Joel Eriksson⁴², Johan G Eriksson^{43

44

45

46}, Karol Estrada^{3

10

47}, Daniel S Evans²², Mary F Feitosa¹⁷, Mao Fu⁴⁸, Christian Gieger^{49

50

51}, Harald Grallert^{49

50

52

53

54}, Vilmundur Gudnason^{41

55}, Launer J Lenore⁵⁶, Caroline Hayward⁵⁷, Albert Hofman^{3

4}, Georg Homuth⁵⁸, Kim M Huffman⁵⁹, Lise B Husted⁶⁰, Thomas Illig^{49

61}, Erik Ingelsson⁶², Till Ittermann⁶³, John-Olov Jansson⁶⁴, Toby Johnson^{16

65

66}, Reiner Biffar⁶⁷, Joanne M Jordan⁶⁸, Antti Jula⁴³, Magnus Karlsson^{8

9}, Kay-Tee Khaw⁶⁹, Tuomas O Kilpeläinen^{70

71

72}, Norman Klopp^{49

73}, Jacqueline S L Kloth³, Daniel L Koller⁴⁰, Jaspal S Kooner^{23

25

74}, William E Kraus⁷⁵, Stephen Kritchevsky⁷⁶, Zoltán Kutalik^{16

66}, Teemu Kuulasmaa⁷⁷, Johanna Kuusisto⁷⁷, Markku Laakso⁷⁷, Jari Lahti⁷⁸, Thomas Lang⁷⁹, Bente L Langdahl⁶⁰, Markus M Lerch⁷, Joshua R Lewis^{80

81}, Christina Lill⁸², Lars Lind⁸³, Cecilia Lindgren⁸⁴, Yongmei Liu⁸⁵, Gregory Livshits^{86

87}, Östen Ljunggren⁸³, Ruth J F Loos^{72

88

89

90}, Mattias Lorentzon⁹¹, Jian'an Luan⁷², Robert N Luben⁷¹, Ida Malkin⁸⁶, Fiona E McGuigan⁸, Carolina Medina-Gomez^{3

10}, Thomas Meitinger^{92

93}, Håkan Melhus⁸³, Dan Mellström⁴², Karl Michaëlsson¹⁹, Braxton D Mitchell^{48

94}, Andrew P Morris^{84

95}, Leif Mosekilde⁶⁰, Maria Nethander⁴², Anne B Newman²¹, Jeffery R O'Connell⁴⁸, Ben A Oostra^{96

97}, Eric S Orwoll⁹⁸, Aarno Palotie^{99

100}, Munro Peacock⁴⁰, Markus Perola^{43

101

102}, Annette Peters^{49

50}, Richard L Prince^{80

103}, Bruce M Psaty^{104

105}, Katri Räikkönen¹⁰⁶, Stuart H Ralston¹⁰⁷, Samuli Ripatti^{11

99

108}, Fernando Rivadeneira^{3

4

10}, John A Robbins¹⁰⁹, Jerome I Rotter¹¹⁰, Igor Rudan²¹, Veikko Salomaa⁴³, Suzanne Satterfield¹¹¹, Sabine Schipf⁶³, Chan Soo Shin²⁹, Albert V Smith^{41

55}, Shad B Smith¹¹², Nicole Soranzo¹¹, Timothy D Spector⁸⁷, Alena Stancáková⁷⁷, Kari Stefansson^{55

113}, Elisabeth Steinhagen-Thiessen³⁶, Lisette Stolk^{3

4}, Elizabeth A Streeten^{48

94}, Unnur Styrkarsdottir¹¹³, Karin M A Swart¹¹⁴, Patricia Thompson¹¹⁵, Cynthia A Thomson²⁷, Gudmar Thorleifsson¹¹³, Unnur Thorsteinsdottir^{55

113}, Emmi Tikkanen^{43

99}, Gregory J Tranah²², André G Uitterlinden^{3

4

10}, Cornelia M van Duijn^{10

97}, Natasja M van Schoor¹¹⁴, Liesbeth Vandenput⁴², Peter Vollenweider¹¹⁶, Henry Völzke⁶³, Jean Wactawski-Wende¹¹⁷, Mark Walker¹¹⁸, Nicholas J Wareham⁷⁰, Dawn Waterworth¹¹⁹, Michael N Weedon¹²⁰, H-Erich Wichmann^{50

121

122}, Elisabeth Widen⁹⁹, Frances M K Williams⁸⁷, James F Wilson²⁰, Nicole C Wright¹²³, Laura M Yerges-Armstrong^{48

119}, Lei Yu¹⁴, Weihua Zhang^{23

25}, Jing Hua Zhao⁷⁰, Yanhua Zhou¹²⁴, Carrie M Nielson⁹⁸, Tamara B Harris⁵⁶, Serkalem Demissie¹²⁴, Douglas P Kiel^{1

5}, Claes Ohlsson⁴²

Affiliations

¹ Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
² Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
³ Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
⁴ Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
⁵ Department of Medicine, Harvard Medical School, Boston, MA.
⁶ Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA.
⁷ Department of Medicine A, University of Greifswald, Greifswald, Germany.
⁸ Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
⁹ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
¹⁰ Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
¹¹ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
¹² NIHR Cambridge Biomedical Research Centre.
¹³ University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
¹⁴ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
¹⁵ Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
¹⁶ University Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
¹⁷ Division of Statistical Genomics, Department of Genetics.
¹⁸ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO.
¹⁹ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²⁰ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom.
²¹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
²² California Pacific Medical Center Research Institute, San Francisco, CA.
²³ Cardiology, Ealing Hospital NHS Trust, London, United Kingdom.
²⁴ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
²⁵ Imperial College Healthcare NHS Trust, London, United Kingdom.
²⁶ NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom.
²⁷ Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
²⁸ Department of Preventive Medicine, Ajou University School of Medicine, Youngtong-Gu, Suwon, Korea.
²⁹ Department of Internal Medicine.
³⁰ Department of Anatomy and Cell Biology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
³¹ Wide River Institute of Immunology, Seoul National University, Hongcheon, Korea.
³² Broad Institute, Cambridge, MA.
³³ Division of Human Nutrition, Wageningen University, AFSG, Wageningen, The Netherlands.
³⁴ Center for Translational and Computational Neuroimmunology, Neurology, Columbia University Medical Center, New York, NY.
³⁵ Cell Circuits Program, Broad Institute, Cambridge, MA.
³⁶ Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
³⁷ Berlin Institute of Health, Berlin, Germany.
³⁸ Regional Center for Neurosensory Disorders, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
³⁹ Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
⁴⁰ Department of Medicine and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
⁴¹ Icelandic Heart Association Holtasmari, Kopavogur, Iceland.
⁴² Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴³ National Institute for Health and Welfare, Helsinki, Finland.
⁴⁴ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁵ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
⁴⁶ Folkhalsan Research Centre, Helsinki, Finland.
⁴⁷ Translational Biology, Biogen, Cambridge, MA.
⁴⁸ Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
⁴⁹ Research Unit of Molecular Epidemiology.
⁵⁰ Institute of Epidemiology II.
⁵¹ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵² CCG Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
⁵³ German Center for Diabetes Research, Neuherberg, Germany.
⁵⁴ CCG Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
⁵⁵ University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
⁵⁶ Laboratory of Epidemiology and Population Sciences, Intramural Research Program, NIA, Bethesda, MD.
⁵⁷ MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, United Kingdom.
⁵⁸ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁵⁹ Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁶⁰ Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark.
⁶¹ Department of Human Genetics, Hannover Medical School, Hanover, Germany.
⁶² Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA.
⁶³ Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
⁶⁴ Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶⁵ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
⁶⁶ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁶⁷ Centre of Oral Health, Department of Prosthetic Dentistry, Gerodontology and Biomaterials, University of Greifswald, Greifswald, Germany.
⁶⁸ Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
⁶⁹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁷⁰ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
⁷¹ Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷² Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷³ Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
⁷⁴ Faculty of Medicine, National Heart & Lung Institute, Cardiovascular Science, Hammersmith Campus, Hammersmith Hospital, Imperial College London, United Kingdom.
⁷⁵ Duke Molecular Physiology Institute and Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁷⁶ Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
⁷⁷ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁷⁸ Helsinki Collegium Advanced Studies, University of Helsinki, Helsinki, Finland.
⁷⁹ Department of Radiology and Biomedical Imaging, and School of Dentistry, UC San Francisco, San Francisco, CA.
⁸⁰ School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
⁸¹ Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
⁸² Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
⁸³ Department. of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁸⁴ Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
⁸⁵ Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
⁸⁶ Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁸⁷ Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Campus, London, United Kingdom.
⁸⁸ The Charles Bronfman Institute of Personalized Medicine.
⁸⁹ Institute of Child Health and Development.
⁹⁰ The Genetics of Obesity and Related Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY.
⁹¹ Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹² Institute of Human Genetics, MRI, Technische Universität München, Munich, Germany.
⁹³ Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁹⁴ Geriatric Research and Education Clinical Center-Veterans Administration Medical Center, Baltimore, MD.
⁹⁵ Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
⁹⁶ Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
⁹⁷ Centre for Medical Systems Biology & Netherlands Consortium on Healthy Aging, Leiden, The Netherlands.
⁹⁸ Oregon Health & Science University, Portland, OR.
⁹⁹ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
¹⁰⁰ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
¹⁰¹ University of Helsinki, Institute for Molecular Medicine, Finland and Diabetes and Obesity Research Program, Helsinki, Finland.
¹⁰² University of Tartu, Estonian Genome Center, Tartu, Estonia.
¹⁰³ Department of Endocrinology and Diabetes, Sir Charles Gardiner Hospital, Perth, Australia.
¹⁰⁴ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA.
¹⁰⁵ Kaiser Permanente Washington Health Research Institute, Seattle, WA.
¹⁰⁶ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
¹⁰⁷ Molecular Medicine Centre, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom.
¹⁰⁸ Hjelt Institute, University of Helsinki, Helsinki, Finland.
¹⁰⁹ Department of Medicine, University California at Davis, Sacramento, CA.
¹¹⁰ Institute for Translational Genomic and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor UCLA Medical Center, Torrance, CA.
¹¹¹ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
¹¹² Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC.
¹¹³ deCODE Genetics, Reykjavik, Iceland.
¹¹⁴ Department of Epidemiology and Biostatistics, and the EMGO+ Institute; VU University Medical Center, Amsterdam, The Netherlands.
¹¹⁵ Department of Pathology, Stony Brook University, Stony Brook, NY.
¹¹⁶ Department of Medicine, Internal Medicine, Lausanne University Hospital and Faculty of Biology and Medicine, Lausanne, Switzerland.
¹¹⁷ Department of Epidemiology and Environmental Health, University at Buffalo, SUNY, Buffalo, NY.
¹¹⁸ Institute of Cellular Medicine (Diabetes), The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
¹¹⁹ Genetics, GlaxoSmithKline, King of Prussia, PA.
¹²⁰ Genetics of Complex Traits, Royal Devon & Exeter Hospital, University of Exeter Medical School, Exeter, United Kingdom.
¹²¹ Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Neuherberg/Munich, Germany.
¹²² Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany.
¹²³ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
¹²⁴ Department of Biostatistics, Boston University School of Public Health, Boston, MA.

PMID: 30721968
PMCID: PMC6500901
DOI: 10.1093/ajcn/nqy272

Disentangling the genetics of lean mass

David Karasik et al. Am J Clin Nutr. 2019.

. 2019 Feb 1;109(2):276-287.

doi: 10.1093/ajcn/nqy272.

Authors

Affiliations

¹ Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, MA.
² Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
³ Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
⁴ Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healthy Aging, Leiden, The Netherlands.
⁵ Department of Medicine, Harvard Medical School, Boston, MA.
⁶ Molecular and Integrative Physiological Sciences Program, Harvard School of Public Health, Boston, MA.
⁷ Department of Medicine A, University of Greifswald, Greifswald, Germany.
⁸ Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
⁹ Department of Orthopedics, Skåne University Hospital, Malmö, Sweden.
¹⁰ Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
¹¹ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom.
¹² NIHR Cambridge Biomedical Research Centre.
¹³ University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom.
¹⁴ Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL.
¹⁵ Lübeck Interdisciplinary Platform for Genome Analytics, University of Lübeck, Lübeck, Germany.
¹⁶ University Institute for Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland.
¹⁷ Division of Statistical Genomics, Department of Genetics.
¹⁸ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO.
¹⁹ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²⁰ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom.
²¹ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
²² California Pacific Medical Center Research Institute, San Francisco, CA.
²³ Cardiology, Ealing Hospital NHS Trust, London, United Kingdom.
²⁴ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
²⁵ Imperial College Healthcare NHS Trust, London, United Kingdom.
²⁶ NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London, United Kingdom.
²⁷ Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
²⁸ Department of Preventive Medicine, Ajou University School of Medicine, Youngtong-Gu, Suwon, Korea.
²⁹ Department of Internal Medicine.
³⁰ Department of Anatomy and Cell Biology, Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, Korea.
³¹ Wide River Institute of Immunology, Seoul National University, Hongcheon, Korea.
³² Broad Institute, Cambridge, MA.
³³ Division of Human Nutrition, Wageningen University, AFSG, Wageningen, The Netherlands.
³⁴ Center for Translational and Computational Neuroimmunology, Neurology, Columbia University Medical Center, New York, NY.
³⁵ Cell Circuits Program, Broad Institute, Cambridge, MA.
³⁶ Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
³⁷ Berlin Institute of Health, Berlin, Germany.
³⁸ Regional Center for Neurosensory Disorders, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC.
³⁹ Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
⁴⁰ Department of Medicine and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
⁴¹ Icelandic Heart Association Holtasmari, Kopavogur, Iceland.
⁴² Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴³ National Institute for Health and Welfare, Helsinki, Finland.
⁴⁴ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁵ Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.
⁴⁶ Folkhalsan Research Centre, Helsinki, Finland.
⁴⁷ Translational Biology, Biogen, Cambridge, MA.
⁴⁸ Program in Personalized and Genomic Medicine, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD.
⁴⁹ Research Unit of Molecular Epidemiology.
⁵⁰ Institute of Epidemiology II.
⁵¹ Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁵² CCG Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
⁵³ German Center for Diabetes Research, Neuherberg, Germany.
⁵⁴ CCG Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
⁵⁵ University of Iceland, Faculty of Medicine, Reykjavik, Iceland.
⁵⁶ Laboratory of Epidemiology and Population Sciences, Intramural Research Program, NIA, Bethesda, MD.
⁵⁷ MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, United Kingdom.
⁵⁸ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁵⁹ Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁶⁰ Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark.
⁶¹ Department of Human Genetics, Hannover Medical School, Hanover, Germany.
⁶² Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA.
⁶³ Institute for Community Medicine, University of Greifswald, Greifswald, Germany.
⁶⁴ Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶⁵ Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.
⁶⁶ Swiss Institute of Bioinformatics, Lausanne, Switzerland.
⁶⁷ Centre of Oral Health, Department of Prosthetic Dentistry, Gerodontology and Biomaterials, University of Greifswald, Greifswald, Germany.
⁶⁸ Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.
⁶⁹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁷⁰ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, United Kingdom.
⁷¹ Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁷² Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY.
⁷³ Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
⁷⁴ Faculty of Medicine, National Heart & Lung Institute, Cardiovascular Science, Hammersmith Campus, Hammersmith Hospital, Imperial College London, United Kingdom.
⁷⁵ Duke Molecular Physiology Institute and Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁷⁶ Sticht Center for Healthy Aging and Alzheimer's Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
⁷⁷ Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
⁷⁸ Helsinki Collegium Advanced Studies, University of Helsinki, Helsinki, Finland.
⁷⁹ Department of Radiology and Biomedical Imaging, and School of Dentistry, UC San Francisco, San Francisco, CA.
⁸⁰ School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
⁸¹ Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, Australia.
⁸² Institute of Neurogenetics, University of Luebeck, Luebeck, Germany.
⁸³ Department. of Medical Sciences, Uppsala University, Uppsala, Sweden.
⁸⁴ Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom.
⁸⁵ Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
⁸⁶ Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
⁸⁷ Department of Twin Research and Genetic Epidemiology, King's College London, St Thomas' Campus, London, United Kingdom.
⁸⁸ The Charles Bronfman Institute of Personalized Medicine.
⁸⁹ Institute of Child Health and Development.
⁹⁰ The Genetics of Obesity and Related Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY.
⁹¹ Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁹² Institute of Human Genetics, MRI, Technische Universität München, Munich, Germany.
⁹³ Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
⁹⁴ Geriatric Research and Education Clinical Center-Veterans Administration Medical Center, Baltimore, MD.
⁹⁵ Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
⁹⁶ Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
⁹⁷ Centre for Medical Systems Biology & Netherlands Consortium on Healthy Aging, Leiden, The Netherlands.
⁹⁸ Oregon Health & Science University, Portland, OR.
⁹⁹ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
¹⁰⁰ Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
¹⁰¹ University of Helsinki, Institute for Molecular Medicine, Finland and Diabetes and Obesity Research Program, Helsinki, Finland.
¹⁰² University of Tartu, Estonian Genome Center, Tartu, Estonia.
¹⁰³ Department of Endocrinology and Diabetes, Sir Charles Gardiner Hospital, Perth, Australia.
¹⁰⁴ Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA.
¹⁰⁵ Kaiser Permanente Washington Health Research Institute, Seattle, WA.
¹⁰⁶ Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
¹⁰⁷ Molecular Medicine Centre, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom.
¹⁰⁸ Hjelt Institute, University of Helsinki, Helsinki, Finland.
¹⁰⁹ Department of Medicine, University California at Davis, Sacramento, CA.
¹¹⁰ Institute for Translational Genomic and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor UCLA Medical Center, Torrance, CA.
¹¹¹ Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN.
¹¹² Center for Translational Pain Medicine, Department of Anesthesiology, Duke University, Durham, NC.
¹¹³ deCODE Genetics, Reykjavik, Iceland.
¹¹⁴ Department of Epidemiology and Biostatistics, and the EMGO+ Institute; VU University Medical Center, Amsterdam, The Netherlands.
¹¹⁵ Department of Pathology, Stony Brook University, Stony Brook, NY.
¹¹⁶ Department of Medicine, Internal Medicine, Lausanne University Hospital and Faculty of Biology and Medicine, Lausanne, Switzerland.
¹¹⁷ Department of Epidemiology and Environmental Health, University at Buffalo, SUNY, Buffalo, NY.
¹¹⁸ Institute of Cellular Medicine (Diabetes), The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, United Kingdom.
¹¹⁹ Genetics, GlaxoSmithKline, King of Prussia, PA.
¹²⁰ Genetics of Complex Traits, Royal Devon & Exeter Hospital, University of Exeter Medical School, Exeter, United Kingdom.
¹²¹ Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Neuherberg/Munich, Germany.
¹²² Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany.
¹²³ Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.
¹²⁴ Department of Biostatistics, Boston University School of Public Health, Boston, MA.

PMID: 30721968
PMCID: PMC6500901
DOI: 10.1093/ajcn/nqy272

Abstract

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.

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Disentangling the genetics of lean mass

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Disentangling the genetics of lean mass

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