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GWAS Study

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

Zillikens MC, Demissie S, Hsu YH et al.

28724990 PubMed ID
GWAS Study Type
73420 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

ZM
Zillikens MC
DS
Demissie S
HY
Hsu YH
YL
Yerges-Armstrong LM
CW
Chou WC
SL
Stolk L
LG
Livshits G
BL
Broer L
JT
Johnson T
KD
Koller DL
KZ
Kutalik Z
LJ
Luan J
MI
Malkin I
RJ
Ried JS
SA
Smith AV
TG
Thorleifsson G
VL
Vandenput L
HZ
Hua Zhao J
ZW
Zhang W
AA
Aghdassi A
ÅK
Åkesson K
AN
Amin N
BL
Baier LJ
BI
Barroso I
BD
Bennett DA
BL
Bertram L
BR
Biffar R
BM
Bochud M
BM
Boehnke M
BI
Borecki IB
BA
Buchman AS
BL
Byberg L
CH
Campbell H
CO
Campos Obanda N
CJ
Cauley JA
CP
Cawthon PM
CH
Cederberg H
CZ
Chen Z
CN
Cho NH
JC
Jin Choi H
CM
Claussnitzer M
CF
Collins F
CS
Cummings SR
DJ
De Jager PL
DI
Demuth I
DR
Dhonukshe-Rutten RAM
DL
Diatchenko L
EG
Eiriksdottir G
EA
Enneman AW
EM
Erdos M
EJ
Eriksson JG
EJ
Eriksson J
EK
Estrada K
ED
Evans DS
FM
Feitosa MF
FM
Fu M
GM
Garcia M
GC
Gieger C
GT
Girke T
GN
Glazer NL
GH
Grallert H
GJ
Grewal J
HB
Han BG
HR
Hanson RL
HC
Hayward C
HA
Hofman A
HE
Hoffman EP
HG
Homuth G
HW
Hsueh WC
HM
Hubal MJ
HA
Hubbard A
HK
Huffman KM
HL
Husted LB
IT
Illig T
IE
Ingelsson E
IT
Ittermann T
JJ
Jansson JO
JJ
Jordan JM
JA
Jula A
KM
Karlsson M
KK
Khaw KT
KT
Kilpeläinen TO
KN
Klopp N
KJ
Kloth JSL
KH
Koistinen HA
KW
Kraus WE
KS
Kritchevsky S
KT
Kuulasmaa T
KJ
Kuusisto J
LM
Laakso M
LJ
Lahti J
LT
Lang T
LB
Langdahl BL
LL
Launer LJ
LJ
Lee JY
LM
Lerch MM
LJ
Lewis JR
LL
Lind L
LC
Lindgren C
LY
Liu Y
LT
Liu T
LY
Liu Y
Ljunggren Ö
LM
Lorentzon M
LR
Luben RN
MW
Maixner W
MF
McGuigan FE
MC
Medina-Gomez C
MT
Meitinger T
MH
Melhus H
MD
Mellström D
MS
Melov S
MK
Michaëlsson K
MB
Mitchell BD
MA
Morris AP
ML
Mosekilde L
NA
Newman A
NC
Nielson CM
OJ
O'Connell JR
OB
Oostra BA
OE
Orwoll ES
PA
Palotie A
PS
Parker SCJ
PM
Peacock M
PM
Perola M
PA
Peters A
PO
Polasek O
PR
Prince RL
RK
Räikkönen K
RS
Ralston SH
RS
Ripatti S
RJ
Robbins JA
RJ
Rotter JI
RI
Rudan I
SV
Salomaa V
SS
Satterfield S
SE
Schadt EE
SS
Schipf S
SL
Scott L
SJ
Sehmi J
SJ
Shen J
SS
Soo Shin C
SG
Sigurdsson G
SS
Smith S
SN
Soranzo N
SA
Stančáková A
SE
Steinhagen-Thiessen E
SE
Streeten EA
SU
Styrkarsdottir U
SK
Swart KMA
TS
Tan ST
TM
Tarnopolsky MA
TP
Thompson P
TC
Thomson CA
TU
Thorsteinsdottir U
TE
Tikkanen E
TG
Tranah GJ
TJ
Tuomilehto J
VS
van Schoor NM
VA
Verma A
VP
Vollenweider P
VH
Völzke H
WJ
Wactawski-Wende J
WM
Walker M
WM
Weedon MN
WR
Welch R
WH
Wichmann HE
WE
Widen E
WF
Williams FMK
WJ
Wilson JF
WN
Wright NC
XW
Xie W
YL
Yu L
ZY
Zhou Y
CJ
Chambers JC
DA
Döring A
VD
van Duijn CM
EM
Econs MJ
GV
Gudnason V
KJ
Kooner JS
PB
Psaty BM
ST
Spector TD
SK
Stefansson K
RF
Rivadeneira F
UA
Uitterlinden AG
WN
Wareham NJ
OV
Ossowski V
WD
Waterworth D
LR
Loos RJF
KD
Karasik D
HT
Harris TB
OC
Ohlsson C
KD
Kiel DP
Chapter II

Abstract

Summary of the research findings

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.

27,488 European ancestry individuals, 842 Old Order Amish individuals

Chapter III

Study Statistics

Key metrics and study information

73420
Total Participants
GWAS
Study Type
Yes
Replicated
42,360 European ancestry individuals, 380 African American individuals, 2,350 Korean ancestry individuals
Replication Participants
East Asian, European, African American or Afro-Caribbean, South Asian
Ancestry
Republic of Korea, U.S., Australia, Germany, Netherlands, Denmark, Finland, Iceland, Sweden, U.K., Croatia, Switzerland, Austria, France, Republic of Ireland, Greece, Italy, Montenegro, Serbia, Spain
Recruitment Country
Chapter IV

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