Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

M Carola Zillikens; Serkalem Demissie; Yi-Hsiang Hsu; Laura M Yerges-Armstrong; Wen-Chi Chou; Lisette Stolk; Gregory Livshits; Linda Broer; Toby Johnson; Daniel L Koller; Zoltán Kutalik; Jian'an Luan; Ida Malkin; Janina S Ried; Albert V Smith; Gudmar Thorleifsson; Liesbeth Vandenput; Jing Hua Zhao; Weihua Zhang; Ali Aghdassi; Kristina Åkesson; Najaf Amin; Leslie J Baier; Inês Barroso; David A Bennett; Lars Bertram; Rainer Biffar; Murielle Bochud; Michael Boehnke; Ingrid B Borecki; Aron S Buchman; Liisa Byberg; Harry Campbell; Natalia Campos Obanda; Jane A Cauley; Peggy M Cawthon; Henna Cederberg; Zhao Chen; Nam H Cho; Hyung Jin Choi; Melina Claussnitzer; Francis Collins; Steven R Cummings; Philip L De Jager; Ilja Demuth; Rosalie A M Dhonukshe-Rutten; Luda Diatchenko; Gudny Eiriksdottir; Anke W Enneman; Mike Erdos; Johan G Eriksson; Joel Eriksson; Karol Estrada; Daniel S Evans; Mary F Feitosa; Mao Fu; Melissa Garcia; Christian Gieger; Thomas Girke; Nicole L Glazer; Harald Grallert; Jagvir Grewal; Bok-Ghee Han; Robert L Hanson; Caroline Hayward; Albert Hofman; Eric P Hoffman; Georg Homuth; Wen-Chi Hsueh; Monica J Hubal; Alan Hubbard; Kim M Huffman; Lise B Husted; Thomas Illig; Erik Ingelsson; Till Ittermann; John-Olov Jansson; Joanne M Jordan; Antti Jula; Magnus Karlsson; Kay-Tee Khaw; Tuomas O Kilpeläinen; Norman Klopp; Jacqueline S L Kloth; Heikki A Koistinen; William E Kraus; Stephen Kritchevsky; Teemu Kuulasmaa; Johanna Kuusisto; Markku Laakso; Jari Lahti; Thomas Lang; Bente L Langdahl; Lenore J Launer; Jong-Young Lee; Markus M Lerch; Joshua R Lewis; Lars Lind; Cecilia Lindgren; Yongmei Liu; Tian Liu; Youfang Liu; Östen Ljunggren; Mattias Lorentzon; Robert N Luben; William Maixner; Fiona E McGuigan; Carolina Medina-Gomez; Thomas Meitinger; Håkan Melhus; Dan Mellström; Simon Melov; Karl Michaëlsson; Braxton D Mitchell; Andrew P Morris; Leif Mosekilde; Anne Newman; Carrie M Nielson; Jeffrey R O'Connell; Ben A Oostra; Eric S Orwoll; Aarno Palotie; Stephen C J Parker; Munro Peacock; Markus Perola; Annette Peters; Ozren Polasek; Richard L Prince; Katri Räikkönen; Stuart H Ralston; Samuli Ripatti; John A Robbins; Jerome I Rotter; Igor Rudan; Veikko Salomaa; Suzanne Satterfield; Eric E Schadt; Sabine Schipf; Laura Scott; Joban Sehmi; Jian Shen; Chan Soo Shin; Gunnar Sigurdsson; Shad Smith; Nicole Soranzo; Alena Stančáková; Elisabeth Steinhagen-Thiessen; Elizabeth A Streeten; Unnur Styrkarsdottir; Karin M A Swart; Sian-Tsung Tan; Mark A Tarnopolsky; Patricia Thompson; Cynthia A Thomson; Unnur Thorsteinsdottir; Emmi Tikkanen; Gregory J Tranah; Jaakko Tuomilehto; Natasja M van Schoor; Arjun Verma; Peter Vollenweider; Henry Völzke; Jean Wactawski-Wende; Mark Walker; Michael N Weedon; Ryan Welch; H-Erich Wichmann; Elisabeth Widen; Frances M K Williams; James F Wilson; Nicole C Wright; Weijia Xie; Lei Yu; Yanhua Zhou; John C Chambers; Angela Döring; Cornelia M van Duijn; Michael J Econs; Vilmundur Gudnason; Jaspal S Kooner; Bruce M Psaty; Timothy D Spector; Kari Stefansson; Fernando Rivadeneira; André G Uitterlinden; Nicholas J Wareham; Vicky Ossowski; Dawn Waterworth; Ruth J F Loos; David Karasik; Tamara B Harris; Claes Ohlsson; Douglas P Kiel; Institute of Neuroscience and Physiology

doi:10.1038/s41467-017-00031-7

Back

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Journal article

Open access

Peer reviewed

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

M Carola Zillikens, Serkalem Demissie, Yi-Hsiang Hsu, Laura M Yerges-Armstrong, Wen-Chi Chou, Lisette Stolk, Gregory Livshits, Linda Broer, Toby Johnson, Daniel L Koller, …

Nature communications, Vol.8(1), pp.80-80

19/07/2017

DOI: https://doi.org/10.1038/s41467-017-00031-7

PMCID: PMC5517526

PMID: 28724990

Abstract

17-Hydroxysteroid Dehydrogenases - genetics

ADAMTS Proteins - genetics

Aldehyde Oxidoreductases - genetics

Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics

Body Composition

Extracellular Matrix Proteins - genetics

Genome-Wide Association Study

Humans

Insulin Receptor Substrate Proteins - genetics

Phenotype

Polymorphism, Single Nucleotide

Quantitative Trait Loci

Regulatory Elements, Transcriptional

Thinness - genetics

Versicans - genetics

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10 ) or suggestively genome wide (p < 2.3 × 10 ). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Files and links (1)

url

https://doi.org/10.1038/s41467-017-00031-7View

Published (Version of record) Open

Metrics

1 Record Views

See more details

Details

Title: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
Creators - without role: M Carola Zillikens - Erasmus MC
Serkalem Demissie - Boston University
Yi-Hsiang Hsu - Hebrew SeniorLife
Laura M Yerges-Armstrong - University of Maryland, Baltimore
Wen-Chi Chou - Hebrew SeniorLife
Lisette Stolk - Erasmus University Rotterdam
Gregory Livshits - King's College London
Linda Broer - Erasmus MC
Toby Johnson - University of Lausanne
Daniel L Koller - Indiana University
Zoltán Kutalik - University of Lausanne
Jian'an Luan - MRC Epidemiology Unit
Ida Malkin - Tel Aviv University
Janina S Ried - Helmholtz Zentrum München
Albert V Smith - Icelandic Heart Association
Gudmar Thorleifsson - deCODE Genetics
Liesbeth Vandenput - University of Gothenburg
Jing Hua Zhao - University of Cambridge
Weihua Zhang - Imperial College London
Ali Aghdassi - University of Greifswald
Kristina Åkesson - Skåne University Hospital
Najaf Amin - Erasmus MC
Leslie J Baier - National Institute of Diabetes and Digestive and Kidney Diseases
Inês Barroso - Wellcome Sanger Institute
David A Bennett - Rush University Medical Center
Lars Bertram - Imperial College London
Rainer Biffar - University of Greifswald
Murielle Bochud - Institute of Social and Preventive Medicine
Michael Boehnke - University of Michigan–Ann Arbor
Ingrid B Borecki - Washington University in St. Louis
Aron S Buchman - Rush University Medical Center
Liisa Byberg - Uppsala University
Harry Campbell - University of Edinburgh
Natalia Campos Obanda - Erasmus MC
Jane A Cauley - University of Pittsburgh
Peggy M Cawthon - California Pacific Medical Center
Henna Cederberg - University of Eastern Finland
Zhao Chen - University of Arizona
Nam H Cho - Ajou University
Hyung Jin Choi - Chungbuk National University Hospital
Melina Claussnitzer - Hebrew SeniorLife
Francis Collins - National Human Genome Research Institute
Steven R Cummings - California Pacific Medical Center
Philip L De Jager - Harvard University
Ilja Demuth - Charité - Universitätsmedizin Berlin
Rosalie A M Dhonukshe-Rutten - Wageningen University & Research
Luda Diatchenko - McGill University
Gudny Eiriksdottir - Icelandic Heart Association
Anke W Enneman - Erasmus University Rotterdam
Mike Erdos - National Human Genome Research Institute
Johan G Eriksson - University of Helsinki
Joel Eriksson - University of Gothenburg
Karol Estrada - Erasmus University Rotterdam
Daniel S Evans - California Pacific Medical Center
Mary F Feitosa - Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St Louis, MO, 63110, USA
Mao Fu - University of Maryland, Baltimore
Melissa Garcia - Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute for Aging, Bethesda, MD, 20892, USA
Christian Gieger - Helmholtz Zentrum München
Thomas Girke - University of California, Riverside
Nicole L Glazer - Boston University
Harald Grallert - Helmholtz Zentrum München
Jagvir Grewal - Ealing Hospital
Bok-Ghee Han - Korea National Institute of Health
Robert L Hanson - National Institute of Diabetes and Digestive and Kidney Diseases
Caroline Hayward - MRC Institute of Genetics and Molecular Medicine
Albert Hofman - Erasmus University Rotterdam
Eric P Hoffman - Binghamton University
Georg Homuth - University of Greifswald
Wen-Chi Hsueh - National Institute of Diabetes and Digestive and Kidney Diseases
Monica J Hubal - George Washington University
Alan Hubbard - University of California, Berkeley
Kim M Huffman - Duke University
Lise B Husted - Aarhus University Hospital
Thomas Illig - Helmholtz Zentrum München
Erik Ingelsson - Stanford University
Till Ittermann - Greifswald University Hospital
John-Olov Jansson - University of Gothenburg
Joanne M Jordan - University of North Carolina at Chapel Hill
Antti Jula - Finnish Institute for Health and Welfare
Magnus Karlsson - Skåne University Hospital
Kay-Tee Khaw - University of Cambridge
Tuomas O Kilpeläinen - Icahn School of Medicine at Mount Sinai
Norman Klopp - Helmholtz Zentrum München
Jacqueline S L Kloth - Erasmus University Rotterdam
Heikki A Koistinen - Finnish Institute for Health and Welfare
William E Kraus - Duke University
Stephen Kritchevsky - Wake Forest University
Teemu Kuulasmaa - University of Eastern Finland
Johanna Kuusisto - Kuopio University Hospital
Markku Laakso - Kuopio University Hospital
Jari Lahti - University of Helsinki
Thomas Lang - University of California, San Francisco
Bente L Langdahl - Aarhus University Hospital
Lenore J Launer - Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute for Aging, Bethesda, MD, 20892, USA
Jong-Young Lee - Korea National Institute of Health
Markus M Lerch - University of Greifswald
Joshua R Lewis - University of Western Australia
Lars Lind - Uppsala University
Cecilia Lindgren - University of Oxford
Yongmei Liu - Wake Forest University
Tian Liu - Max Planck Institute for Human Development
Youfang Liu - University of North Carolina at Chapel Hill
Östen Ljunggren - Uppsala University
Mattias Lorentzon - University of Gothenburg
Robert N Luben - University of Cambridge
William Maixner - University of North Carolina at Chapel Hill
Fiona E McGuigan - Lund University
Carolina Medina-Gomez - Erasmus MC
Thomas Meitinger - Helmholtz Zentrum München
Håkan Melhus - Uppsala University
Dan Mellström - University of Gothenburg
Simon Melov - Leonard Davis School of Gerontology, University of Southern California, LA, CA, 90089, USA
Karl Michaëlsson - Uppsala University
Braxton D Mitchell - Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD, 21201, USA
Andrew P Morris - University of Liverpool
Leif Mosekilde - Aarhus University Hospital
Anne Newman - University of Pittsburgh
Carrie M Nielson - Oregon Health & Science University
Jeffrey R O'Connell - Genomic
Ben A Oostra - Centre for Medical Systems Biology and Netherlands Consortium on Healthy Aging, Leiden, RC2300, The Netherlands
Eric S Orwoll - Oregon Health & Science University
Aarno Palotie - University of Helsinki
Stephen C J Parker - University of Michigan–Ann Arbor
Munro Peacock - Indiana University
Markus Perola - University of Tartu
Annette Peters - Helmholtz Zentrum München
Ozren Polasek - University of Split
Richard L Prince - Department of Endocrinology and Diabetes, Sir Charles Gardiner Hospital, Perth, 6009, Australia
Katri Räikkönen - University of Helsinki
Stuart H Ralston - MRC Institute of Genetics and Molecular Medicine
Samuli Ripatti - Wellcome Sanger Institute
John A Robbins - Department of Medicine, University of California at Davis, Sacramento, CA, 95817, USA
Jerome I Rotter - The Lundquist Institute
Igor Rudan - University of Edinburgh
Veikko Salomaa - National Institute for Health and Welfare, Helsinki, 00271, Finland
Suzanne Satterfield - University of Tennessee Health Science Center
Eric E Schadt - Icahn School of Medicine at Mount Sinai
Sabine Schipf - University of Greifswald
Laura Scott - University of Michigan–Ann Arbor
Joban Sehmi - Imperial College London
Jian Shen - Oregon Health & Science University
Chan Soo Shin - Seoul National University
Gunnar Sigurdsson - National University Hospital of Iceland
Shad Smith - Center for Translational Pain Medicine, Department of Anesthiology, Duke University Medical Center, Durham, NC, 27110, USA
Nicole Soranzo - Wellcome Sanger Institute
Alena Stančáková - University of Eastern Finland
Elisabeth Steinhagen-Thiessen - Humboldt-Universität zu Berlin
Elizabeth A Streeten - Geriatric Research and Education Clinical Center (GRECC) - Veterans Administration Medical Center, Baltimore, MD, 21201, USA
Unnur Styrkarsdottir - deCODE Genetics
Karin M A Swart - Department of Epidemiology and Biostatistics, and the EMGO Institute, VU University Medical Center, Amsterdam, BT1081, The Netherlands
Sian-Tsung Tan - Imperial College London
Mark A Tarnopolsky - McMaster University
Patricia Thompson - Stony Brook School
Cynthia A Thomson - University of Arizona
Unnur Thorsteinsdottir - deCODE Genetics
Emmi Tikkanen - MRC Institute of Genetics and Molecular Medicine
Gregory J Tranah - California Pacific Medical Center Research Institute, San Francisco, CA, 94107, USA
Jaakko Tuomilehto - Dasman Diabetes Institute
Natasja M van Schoor - Department of Epidemiology and Biostatistics, and the EMGO Institute, VU University Medical Center, Amsterdam, BT1081, The Netherlands
Arjun Verma - Ealing Hospital NHS Trust
Peter Vollenweider - Department of Medicine and Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, CH-1011, Switzerland
Henry Völzke - University of Greifswald
Jean Wactawski-Wende - University at Buffalo, State University of New York
Mark Walker - Newcastle University
Michael N Weedon - University of Exeter
Ryan Welch - University of Michigan–Ann Arbor
H-Erich Wichmann - Technical University of Munich
Elisabeth Widen - University of Helsinki
Frances M K Williams - King's College London
James F Wilson - University of Edinburgh
Nicole C Wright - University of Alabama at Birmingham
Weijia Xie - University of Exeter
Lei Yu - Rush University Medical Center
Yanhua Zhou - Boston University
John C Chambers - Imperial College Healthcare NHS Trust
Angela Döring - Helmholtz Zentrum München
Cornelia M van Duijn - Centre for Medical Systems Biology and Netherlands Consortium on Healthy Aging, Leiden, RC2300, The Netherlands
Michael J Econs - Indiana University
Vilmundur Gudnason - University of Iceland
Jaspal S Kooner - Imperial College Healthcare NHS Trust
Bruce M Psaty - Kaiser Permanente Washington Health Research Institute
Timothy D Spector - King's College London
Kari Stefansson - deCODE Genetics
Fernando Rivadeneira - Erasmus MC
André G Uitterlinden - Erasmus MC
Nicholas J Wareham - University of Cambridge
Vicky Ossowski - National Institute of Diabetes and Digestive and Kidney Diseases
Dawn Waterworth - GlaxoSmithKline
Ruth J F Loos - Icahn School of Medicine at Mount Sinai
David Karasik - Bar-Ilan University
Tamara B Harris - Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute for Aging, Bethesda, MD, 20892, USA
Claes Ohlsson - University of Gothenburg
Douglas P Kiel - Beth Israel Deaconess Medical Center
Institute of Neuroscience and Physiology
Publication Details: Nature communications, Vol.8(1), pp.80-80
Grant note: R01 HL087700 / NHLBI NIH HHS SP/04/002 / British Heart Foundation P30 DK048520 / NIDDK NIH HHS MR/N003284/1 / Medical Research Council R01 AG005394 / NIA NIH HHS ZIA HG000024 / Intramural NIH HHS HHSN268200782096C / NHGRI NIH HHS R21 AR056405 / NIAMS NIH HHS R56 AG023629 / NIA NIH HHS P30 DK020541 / NIDDK NIH HHS N01 HC045133 / NHLBI NIH HHS R01 HL103612 / NHLBI NIH HHS UL1 TR002369 / NCATS NIH HHS N01 AG062106 / NIA NIH HHS R01 HL080295 / NHLBI NIH HHS WT098017 / Wellcome Trust R01 AG027576 / NIA NIH HHS N01 HC085084 / NHLBI NIH HHS UL1 RR033176 / NCRR NIH HHS MC_PC_U127561128 / Medical Research Council P30 DK063491 / NIDDK NIH HHS R01 HL087652 / NHLBI NIH HHS U01 AG042168 / NIA NIH HHS Wellcome Trust U01 HL080295 / NHLBI NIH HHS R01 HL120393 / NHLBI NIH HHS R01 AR035584 / NIAMS NIH HHS N01HC85083 / NHLBI NIH HHS N01 HC015103 / NHLBI NIH HHS R01 HL117078 / NHLBI NIH HHS R01 AG023629 / NIA NIH HHS 14136 / Cancer Research UK R01 AG032098 / NIA NIH HHS P60 AR030701 / NIAMS NIH HHS U01 AG042140 / NIA NIH HHS U01 HL072515 / NHLBI NIH HHS HHSN268201200036C / NHLBI NIH HHS U01 HL130114 / NHLBI NIH HHS S10 OD016290 / NIH HHS RC2 AR058973 / NIAMS NIH HHS R01 AG015928 / NIA NIH HHS U24 AG051129 / NIA NIH HHS N01HC85082 / NHLBI NIH HHS R01 AG005407 / NIA NIH HHS R01 AG017917 / NIA NIH HHS R01 DK089256 / NIDDK NIH HHS U01 HL084756 / NHLBI NIH HHS P30 DK020572 / NIDDK NIH HHS M01 RR000750 / NCRR NIH HHS N01WH22110 / WHI NIH HHS G1000143 / Medical Research Council U01 AG027810 / NIA NIH HHS N01HC85079 / NHLBI NIH HHS N01 AG062103 / NIA NIH HHS N01 HC085085 / NHLBI NIH HHS UL1 TR001881 / NCATS NIH HHS U01 AG042124 / NIA NIH HHS R01 AG027574 / NIA NIH HHS U01 AG042139 / NIA NIH HHS R01 AR035583 / NIAMS NIH HHS CZB/4/710 / Chief Scientist Office R01 AR057118 / NIAMS NIH HHS WT098051 / Wellcome Trust R01 DK075681 / NIDDK NIH HHS R01 HL088215 / NHLBI NIH HHS P60 AR049465 / NIAMS NIH HHS U01 AG042145 / NIA NIH HHS R56 AG020098 / NIA NIH HHS MC_UU_12015/1 / Medical Research Council N01HC75150 / NHLBI NIH HHS R01 AG020098 / NIA NIH HHS P30 DK072488 / NIDDK NIH HHS N01HC25195 / NHLBI NIH HHS UL1 TR000128 / NCATS NIH HHS N01HC85081 / NHLBI NIH HHS U01 AR066160 / NIAMS NIH HHS R01 AG024480 / NIA NIH HHS G0401527 / Medical Research Council U01 GM074518 / NIGMS NIH HHS N01HC85086 / NHLBI NIH HHS U01 AG042143 / NIA NIH HHS R01 AG015819 / NIA NIH HHS N01HC85080 / NHLBI NIH HHS R01 HL088119 / NHLBI NIH HHS UL1 TR000124 / NCATS NIH HHS CZB/4/276 / Chief Scientist Office R01 AG027058 / NIA NIH HHS N01HC55222 / NHLBI NIH HHS R01 AR046838 / NIAMS NIH HHS N01AG12100 / NIA NIH HHS N01 AG062101 / NIA NIH HHS CIHR U01 HL120393 / NHLBI NIH HHS R01 AG041517 / NIA NIH HHS R01 HL105756 / NHLBI NIH HHS U01 DK062370 / NIDDK NIH HHS F32 AR059469 / NIAMS NIH HHS N01 HC035129 / NHLBI NIH HHS R01 AR041398 / NIAMS NIH HHS R00 DK099240 / NIDDK NIH HHS R01 AR035582 / NIAMS NIH HHS
Identifiers: 9937065708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article