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

Journal article
Authors M. C. Zillikens
S. Demissie
Y. H. Hsu
L. M. Yerges-Armstrong
W. C. Chou
L. Stolk
G. Livshits
L. Broer
T. Johnson
D. L. Koller
Z. Kutalik
J. Luan
I. Malkin
J. S. Ried
A. V. Smith
G. Thorleifsson
Liesbeth Vandenput
J. H. Zhao
W. H. Zhang
A. Aghdassi
K. Akesson
N. Amin
L. J. Baier
I. Barroso
D. A. Bennett
L. Bertram
R. Biffar
M. Bochud
M. Boehnke
I. B. Borecki
A. S. Buchman
L. Byberg
H. Campbell
N. C. Obanda
J. A. Cauley
P. M. Cawthon
H. Cederberg
Z. Chen
N. H. Cho
H. J. Choi
M. Claussnitzer
F. Collins
S. R. Cummings
P. L. De Jager
I. Demuth
R. A. M. Dhonukshe-Rutten
L. Diatchenko
G. Eiriksdottir
A. W. Enneman
M. Erdos
J. G. Eriksson
Joel Eriksson
K. Estrada
D. S. Evans
M. F. Feitosa
M. Fu
M. Garcia
C. Gieger
T. Girke
N. L. Glazer
H. Grallert
J. Grewal
B. G. Han
R. L. Hanson
C. Hayward
A. Hofman
E. P. Hoffman
G. Homuth
W. C. Hsueh
M. J. Hubal
A. Hubbard
K. M. Huffman
L. B. Husted
T. Illig
E. Ingelsson
T. Ittermann
John-Olov Jansson
J. M. Jordan
A. Jula
M. Karlsson
K. T. Khaw
T. O. Kilpainen
N. Klopp
J. S. L. Kloth
H. A. Koistinen
W. E. Kraus
S. Kritchevsky
T. Kuulasmaa
J. Kuusisto
M. Laakso
J. Lahti
T. Lang
B. L. Langdahl
L. J. Launer
J. Y. Lee
M. M. Lerch
J. R. Lewis
L. Lind
C. Lindgren
Y. M. Liu
T. Liu
Y. F. Liu
O. Ljunggren
Mattias Lorentzon
R. N. Luben
W. Maixner
F. E. McGuigan
C. Medina-Gomez
T. Meitinger
H. Melhus
Dan Mellström
S. Melov
K. Michaelsson
B. D. Mitchell
A. P. Morris
L. Mosekilde
A. Newman
C. M. Nielson
J. R. O'Connell
B. A. Oostra
E. S. Orwoll
A. Palotie
S. Parker
M. Peacock
M. Perola
A. Peters
O. Polasek
R. L. Prince
K. Raikkonen
S. H. Ralston
S. Ripatti
J. A. Robbins
J. I. Rotter
I. Rudan
V. Salomaa
S. Satterfield
E. E. Schadt
S. Schipf
L. Scott
J. Sehmi
J. Shen
C. S. Shin
G. Sigurdsson
S. Smith
N. Soranzo
A. Stancakova
E. Steinhagen-Thiessen
E. A. Streeten
U. Styrkarsdottir
K. M. A. Swart
S. T. Tan
M. A. Tarnopolsky
P. Thompson
C. A. Thomson
U. Thorsteinsdottir
E. Tikkanen
G. J. Tranah
J. Tuomilehto
N. M. van Schoor
A. Verma
P. Vollenweider
H. Volzke
J. Wactawski-Wende
M. Walker
M. N. Weedon
R. Welch
H. E. Wichman
E. Widen
F. M. K. Williams
J. F. Wilson
N. C. Wright
W. J. Xie
L. Yu
Y. H. Zhou
J. C. Chambers
A. Doring
C. M. van Duijn
M. J. Econs
V. Gudnason
J. S. Kooner
B. M. Psaty
T. D. Spector
K. Stefansson
F. Rivadeneira
A. G. Uitterlinden
N. J. Wareham
V. Ossowski
D. Waterworth
R. J. F. Loos
D. Karasik
T. B. Harris
Claes Ohlsson
D. P. Kiel
V. P. Nada
Published in Nature Communications
Volume 8
Issue 1
ISSN 2041-1723
Publication year 2017
Published at Institute of Neuroscience and Physiology
Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Language en
Links dx.doi.org/10.1038/s41467-017-00031...
Keywords SKELETAL-MUSCLE MASS, BONE-MINERAL DENSITY, PHYSICAL-DISABILITY, INSULIN-RESISTANCE, GENE-EXPRESSION, UNITED-STATES, HUMAN HEIGHT, VARIANTS, OBESITY, SARCOPENIA,
Subject categories Gastroenterology and Hepatology

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

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