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Meta-Analysis
. 2017 Jul 19;8(1):80.
doi: 10.1038/s41467-017-00031-7.

Large Meta-Analysis of Genome-Wide Association Studies Identifies Five Loci for Lean Body Mass

M Carola Zillikens  1   2 Serkalem Demissie  3 Yi-Hsiang Hsu  4   5   6 Laura M Yerges-Armstrong  7 Wen-Chi Chou  4   5   8 Lisette Stolk  1   2 Gregory Livshits  9   10 Linda Broer  11 Toby Johnson  12   13   14 Daniel L Koller  15 Zoltán Kutalik  12   13   14 Jian'an Luan  16 Ida Malkin  9 Janina S Ried  17 Albert V Smith  18   19 Gudmar Thorleifsson  20 Liesbeth Vandenput  21 Jing Hua Zhao  16 Weihua Zhang  22   23 Ali Aghdassi  24 Kristina Åkesson  25   26 Najaf Amin  11 Leslie J Baier  27 Inês Barroso  28   29   30 David A Bennett  31 Lars Bertram  32   33 Rainer Biffar  34 Murielle Bochud  14 Michael Boehnke  35 Ingrid B Borecki  36   37 Aron S Buchman  31 Liisa Byberg  38 Harry Campbell  39 Natalia Campos Obanda  1 Jane A Cauley  40 Peggy M Cawthon  41 Henna Cederberg  42 Zhao Chen  43 Nam H Cho  44 Hyung Jin Choi  45   46 Melina Claussnitzer  4   5   8   47   48   49 Francis Collins  50 Steven R Cummings  41 Philip L De Jager  5   51   52 Ilja Demuth  53   54 Rosalie A M Dhonukshe-Rutten  55 Luda Diatchenko  56   57 Gudny Eiriksdottir  18 Anke W Enneman  1 Mike Erdos  50 Johan G Eriksson  58   59   60   61   62 Joel Eriksson  21 Karol Estrada  1   11 Daniel S Evans  41 Mary F Feitosa  36 Mao Fu  7 Melissa Garcia  63 Christian Gieger  17   64   65 Thomas Girke  66   67 Nicole L Glazer  68 Harald Grallert  17   64   67   69   70   71 Jagvir Grewal  23   72 Bok-Ghee Han  73 Robert L Hanson  27 Caroline Hayward  74 Albert Hofman  2   11 Eric P Hoffman  75 Georg Homuth  76 Wen-Chi Hsueh  27 Monica J Hubal  77   78 Alan Hubbard  79 Kim M Huffman  80 Lise B Husted  81 Thomas Illig  64   82   83 Erik Ingelsson  84   85 Till Ittermann  86 John-Olov Jansson  87 Joanne M Jordan  88 Antti Jula  62 Magnus Karlsson  89 Kay-Tee Khaw  90 Tuomas O Kilpeläinen  16   91   92 Norman Klopp  64   83 Jacqueline S L Kloth  1 Heikki A Koistinen  93   94   95   96 William E Kraus  97 Stephen Kritchevsky  98 Teemu Kuulasmaa  42 Johanna Kuusisto  42 Markku Laakso  42 Jari Lahti  99 Thomas Lang  100 Bente L Langdahl  81 Lenore J Launer  63 Jong-Young Lee  73 Markus M Lerch  24 Joshua R Lewis  101   102 Lars Lind  84 Cecilia Lindgren  103 Yongmei Liu  104 Tian Liu  105   106 Youfang Liu  88 Östen Ljunggren  84 Mattias Lorentzon  21 Robert N Luben  90 William Maixner  57 Fiona E McGuigan  25 Carolina Medina-Gomez  1   11 Thomas Meitinger  48   107 Håkan Melhus  84 Dan Mellström  21 Simon Melov  108   109 Karl Michaëlsson  38 Braxton D Mitchell  7   110 Andrew P Morris  103   111 Leif Mosekilde  81 Anne Newman  112 Carrie M Nielson  113 Jeffrey R O'Connell  7 Ben A Oostra  114   115 Eric S Orwoll  113 Aarno Palotie  116   117 Stephen C J Parker  118 Munro Peacock  119 Markus Perola  62   116   120   121 Annette Peters  17   64 Ozren Polasek  122 Richard L Prince  101   123 Katri Räikkönen  99 Stuart H Ralston  124 Samuli Ripatti  116   125   28 John A Robbins  126 Jerome I Rotter  127 Igor Rudan  39 Veikko Salomaa  62 Suzanne Satterfield  128 Eric E Schadt  129 Sabine Schipf  86 Laura Scott  35 Joban Sehmi  23   72 Jian Shen  113 Chan Soo Shin  45 Gunnar Sigurdsson  19   130 Shad Smith  131 Nicole Soranzo  28 Alena Stančáková  42 Elisabeth Steinhagen-Thiessen  53 Elizabeth A Streeten  7   132 Unnur Styrkarsdottir  20 Karin M A Swart  133 Sian-Tsung Tan  23   72 Mark A Tarnopolsky  134 Patricia Thompson  135 Cynthia A Thomson  43 Unnur Thorsteinsdottir  19   20 Emmi Tikkanen  62   116   124 Gregory J Tranah  41 Jaakko Tuomilehto  61   136   137   138 Natasja M van Schoor  133 Arjun Verma  23 Peter Vollenweider  139 Henry Völzke  86 Jean Wactawski-Wende  140 Mark Walker  141 Michael N Weedon  142 Ryan Welch  35 H-Erich Wichmann  17   143   144 Elisabeth Widen  116 Frances M K Williams  10 James F Wilson  39   74 Nicole C Wright  145 Weijia Xie  142 Lei Yu  31 Yanhua Zhou  3 John C Chambers  22   23   146   147 Angela Döring  17   148 Cornelia M van Duijn  11   115 Michael J Econs  149 Vilmundur Gudnason  18   19 Jaspal S Kooner  23   72   147 Bruce M Psaty  150   151 Timothy D Spector  10 Kari Stefansson  19   20 Fernando Rivadeneira  1   2   11 André G Uitterlinden  1   2   11 Nicholas J Wareham  16 Vicky Ossowski  27 Dawn Waterworth  152 Ruth J F Loos  16   153   154   155   156 David Karasik  4   5   157 Tamara B Harris  63 Claes Ohlsson  21 Douglas P Kiel  158   159   160
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Free PMC article
Meta-Analysis

Large Meta-Analysis of Genome-Wide Association Studies Identifies Five Loci for Lean Body Mass

M Carola Zillikens et al. Nat Commun. .
Free PMC article

Erratum in

  • Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.
    Zillikens MC, Demissie S, Hsu YH, Yerges-Armstrong LM, Chou WC, Stolk L, Livshits G, Broer L, Johnson T, Koller DL, Kutalik Z, Luan J, Malkin I, Ried JS, Smith AV, Thorleifsson G, Vandenput L, Hua Zhao J, Zhang W, Aghdassi A, Åkesson K, Amin N, Baier LJ, Barroso I, Bennett DA, Bertram L, Biffar R, Bochud M, Boehnke M, Borecki IB, Buchman AS, Byberg L, Campbell H, Campos Obanda N, Cauley JA, Cawthon PM, Cederberg H, Chen Z, Cho NH, Jin Choi H, Claussnitzer M, Collins F, Cummings SR, De Jager PL, Demuth I, Dhonukshe-Rutten RAM, Diatchenko L, Eiriksdottir G, Enneman AW, Erdos M, Eriksson JG, Eriksson J, Estrada K, Evans DS, Feitosa MF, Fu M, Garcia M, Gieger C, Girke T, Glazer NL, Grallert H, Grewal J, Han BG, Hanson RL, Hayward C, Hofman A, Hoffman EP, Homuth G, Hsueh WC, Hubal MJ, Hubbard A, Huffman KM, Husted LB, Illig T, Ingelsson E, Ittermann T, Jansson JO, Jordan JM, Jula A, Karlsson M, Khaw KT, Kilpeläinen TO, Klopp N, Kloth JSL, Koistinen HA, Kraus WE, Kritchevsky S, Kuulasmaa T, Kuusisto J, Laakso M, Lahti J, Lang T, Langdahl BL, Launer LJ, Lee JY, Lerch MM, Lewis JR, Lind L, Lindgren C, Liu Y, Liu T, Liu Y, Ljunggren Ö, Lorentzon M, Luben RN, Maixner W, McGuigan FE, Medina-Gomez C, Meitinger T, Melhus H, Mellström D, Melov S, Michaëlsson K, Mitchell BD, Morris AP, Mosekilde L, Newman A, Nielson CM, O'Connell JR, Oostra BA, Orwoll ES, Palotie A, Parker SCJ, Peacock M, Perola M, Peters A, Polasek O, Prince RL, Räikkönen K, Ralston SH, Ripatti S, Robbins JA, Rotter JI, Rudan I, Salomaa V, Satterfield S, Schadt EE, Schipf S, Scott L, Sehmi J, Shen J, Soo Shin C, Sigurdsson G, Smith S, Soranzo N, Stančáková A, Steinhagen-Thiessen E, Streeten EA, Styrkarsdottir U, Swart KMA, Tan ST, Tarnopolsky MA, Thompson P, Thomson CA, Thorsteinsdottir U, Tikkanen E, Tranah GJ, Tuomilehto J, van Schoor NM, Verma A, Vollenweider P, Völzke H, Wactawski-Wende J, Walker M, Weedon MN, Welch R, Wichmann HE, Widen E, Williams FMK, Wilson JF, Wright NC, Xie W, Yu L, Zhou Y, Chambers JC, Döring A, van Duijn CM, Econs MJ, Gudnason V, Kooner JS, Psaty BM, Spector TD, Stefansson K, Rivadeneira F, Uitterlinden AG, Wareham NJ, Ossowski V, Waterworth D, Loos RJF, Karasik D, Harris TB, Ohlsson C, Kiel DP. Zillikens MC, et al. Nat Commun. 2017 Nov 7;8(1):1414. doi: 10.1038/s41467-017-01008-2. Nat Commun. 2017. PMID: 29116125 Free PMC article.

Abstract

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 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). 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.

Conflict of interest statement

The authors declare no competing financial interests.

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