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.
Original language | English |
---|---|
Article number | 80 |
Journal | Nature communications |
Volume | 8 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Dec 2017 |
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In: Nature communications, Vol. 8, No. 1, 80, 01.12.2017.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
AU - Zillikens, M. Carola
AU - Demissie, Serkalem
AU - Hsu, Yi Hsiang
AU - Yerges-Armstrong, Laura M.
AU - Chou, Wen Chi
AU - Stolk, Lisette
AU - Livshits, Gregory
AU - Broer, Linda
AU - Johnson, Toby
AU - Koller, Daniel L.
AU - Kutalik, Zoltán
AU - Luan, Jian'an
AU - Malkin, Ida
AU - Ried, Janina S.
AU - Smith, Albert V.
AU - Thorleifsson, Gudmar
AU - Vandenput, Liesbeth
AU - Hua Zhao, Jing
AU - Zhang, Weihua
AU - Aghdassi, Ali
AU - Åkesson, Kristina
AU - Amin, Najaf
AU - Baier, Leslie J.
AU - Barroso, Inês
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AU - Bertram, Lars
AU - Biffar, Rainer
AU - Bochud, Murielle
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AU - Borecki, Ingrid B.
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AU - Campbell, Harry
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AU - Chen, Zhao
AU - Cho, Nam H.
AU - Jin Choi, Hyung
AU - Claussnitzer, Melina
AU - Collins, Francis S.
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AU - DIatchenko, Luda
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AU - Enneman, Anke W.
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AU - Eriksson, Joel
AU - Estrada, Karol
AU - Evans, Daniel S.
AU - Feitosa, Mary F.
AU - Fu, Mao
AU - Garcia, Melissa E.
AU - Gieger, Christian
AU - Girke, Thomas
AU - Glazer, Nicole L.
AU - Grallert, Harald
AU - Grewal, Jagvir
AU - Han, Bok-Ghee
AU - Hanson, Robert L.
AU - Hayward, Caroline
AU - Hofman, Albert
AU - Hoffman, Eric P.
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AU - Khaw, Kay-Tee
AU - Kilpelaïnen, Tuomas O.
AU - Klopp, Norman
AU - Kloth, Jacqueline S.L.
AU - Koistinen, Heikki A.
AU - Kraus, William E.
AU - Kritchevsky, Stephen B.
AU - Kuulasmaa, Teemu
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Lahti, Jari
AU - Lang, Thomas F.
AU - Langdahl, Bente L.
AU - Launer, Lenore J.
AU - Lee, Jong-Young
AU - Lerch, Markus M.
AU - Lewis, Joshua R.
AU - Lind, Lars
AU - Lindgren, Cecilia M.
AU - Liu, Yongmei
AU - Liu, Tian
AU - Liu, Youfang
AU - Ljunggren, Östen
AU - Lorentzon, Mattias
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AU - Maixner, William
AU - McGuigan, Fiona E.
AU - Medina-Gomez, Carolina
AU - Meitinger, Thomas
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AU - Mitchell, Braxton D.
AU - Morris, Andrew P.
AU - Mosekilde, Leif
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AU - Peters, Annette
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AU - Prince, Richard L.
AU - Raïkkönen, Katri
AU - Ralston, Stuart H.
AU - Ripatti, Samuli
AU - Robbins, John A.
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Salomaa, Veikko
AU - Satterfield, Suzanne
AU - Schadt, Eric E
AU - Schipf, Sabine
AU - Scott, Laura
AU - Sehmi, Joban
AU - Shen, Jian
AU - Soo Shin, Chan
AU - Sigurdsson, Gunnar
AU - Smith, Shad
AU - Soranzo, Nicole
AU - Stančáková, Alena
AU - Steinhagen-Thiessen, Elisabeth
AU - Streeten, Elizabeth A.
AU - Styrkarsdottir, Unnur
AU - Swart, Karin M.A.
AU - Tan, Sian-Tsung
AU - Tarnopolsky, Mark A.
AU - Thompson, Patricia
AU - Thomson, Cynthia A.
AU - Thorsteinsdottir, Unnur
AU - Tikkanen, Emmi
AU - Tranah, Gregory J.
AU - Tuomilehto, Jaakko
AU - Van Schoor, Natasja M.
AU - Verma, Arjun
AU - Vollenweider, Peter
AU - Völzke, Henry
AU - Wactawski-Wende, Jean
AU - Walker, Mark J.
AU - Weedon, Michael N.
AU - Welch, Ryan
AU - Wichman, H. Erich
AU - Widen, Elisabeth
AU - Williams, Frances M.K.
AU - Wilson, James F.
AU - Wright, Nicole C.
AU - Xie, Weijia
AU - Yu, Lei
AU - Zhou, Yanhua
AU - Chambers, John C.
AU - Döring, Angela
AU - van Duijn, Cornelia M.
AU - Econs, Michael J.
AU - Gudnason, Vilmundur
AU - Kooner, Jaspal S.
AU - Psaty, Bruce M.
AU - Spector, Timothy D.
AU - Stefansson, Kari
AU - Rivadeneira, Fernando
AU - Uitterlinden, André G.
AU - Wareham, Nicholas J.
AU - Ossowski, Vicky
AU - Waterworth, Dawn
AU - Loos, Ruth J. F.
AU - Karasik, David
AU - Harris, Tamara B.
AU - Ohlsson, Claes
AU - Kiel, Douglas P.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85025138148&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-017-00031-7
DO - https://doi.org/10.1038/s41467-017-00031-7
M3 - Article
C2 - 28724990
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 80
ER -