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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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. / Zillikens, M. Carola; Demissie-Banjaw, Serkalem; Hsu, Yi-Hsiang; Yerges-Armstrong, Laura M.; Chou, Wen Chi; Stolk, Lisette; Livshits, Gregory; Broer, Linda; Johnson, Toby; Koller, Daniel L.; Kutalik, Zoltán; Luan, Jian'An; Malkin, Ida; Ried, Janina S.; Smith, Albert Vernon; Thorleifsson, Gudmar; Vandenput, Liesbeth; Hua Zhao, Jing; Zhang, Weihua; Aghdassi, Ali; Åkesson, Kristina; Amin, Najaf; Baier, Leslie J.; Barroso, Inês; Bennett, David A.; Bertram, Lars; Biffar, Rainer; Bochud, Murielle; Boehnke, Michael; Borecki, Ingrid B.; Buchman, Aron S.; Byberg, Liisa; Campbell, Harry; Campos Obanda, Natalia; Cauley, Jane A.; Cawthon, Peggy M.; Cederberg, Henna; Chen, Zhao; Cho, Nam H.; Jin Choi, Hyung; Claussnitzer, Melina; Collins, Francis S.; Cummings, Steven R.; De Jager, Philip L.; Demuth, Ilja; Dhonukshe-Rutten, Rosalie A.M.; DIatchenko, Luda; Eiriksdottir, Gudny; Enneman, Anke W.; Erdos, Mike; Eriksson, Johan G.; Eriksson, Joel; Estrada, Karol; Evans, Daniel S.; Feitosa, Mary F.; Fu, Mao; Garcia, Melissa; Gieger, Christian; Girke, Thomas; Glazer, Nicole L.; Grallert, Harald; Grewal, Jagvir; Han, Bok Ghee; Hanson, Robert L.; Hayward, Caroline; Hofman, Albert; Hoffman, Eric P.; Homuth, Georg; Hsueh, Wen Chi; Hubal, Monica J.; Hubbard, Alan; Huffman, Kim M.; Husted, Lise Bjerre; Illig, Thomas; Ingelsson, Erik; Ittermann, Till; Jansson, John Olov; Jordan, Joanne M.; Jula, Antti; Karlsson, Magnus; Khaw, Kay Tee; Kilpelaïnen, Tuomas O.; Klopp, Norman; Kloth, Jacqueline S.L.; Koistinen, Heikki A.; Kraus, William E.; Kritchevsky, Stephen; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku; Lahti, Jari; Lang, Thomas; Langdahl, Bente Lomholt; Launer, Lenore J.; Lee, Jong Young; Lerch, Markus M.; Lewis, Joshua R.; Lind, Lars; Lindgren, Cecilia M.; Liu, Yongmei; Liu, Tian; Liu, Youfang; Ljunggren, Östen; Lorentzon, Mattias; Luben, Robert N; Maixner, William; McGuigan, Fiona E.; Medina-Gomez, Carolina; Meitinger, Thomas; Melhus, Håkan; Mellström, Dan; Melov, Simon; Michaëlsson, Karl; Mitchell, Braxton D.; Morris, Andrew P.; Mosekilde, Leif; Newman, Anne; Nielson, Carrie M.; O'connell, Jeffrey R.; Oostra, Ben A.; Orwoll, Eric S.; Palotie, Aarno; Parker, Stephan; Peacock, Munro; Perola, Markus; Peters, Annette; Polasek, Ozren; Prince, Richard L.; Raïkkönen, Katri; Ralston, Stuart H.; Ripatti, Samuli; Robbins, John A.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Satterfield, Suzanne; Schadt, Eric E.; Schipf, Sabine; Scott, Laura J.; Sehmi, Joban S.; Shen, Jian; Soo Shin, Chan; Sigurdsson, Gunnar; Smith, Shad; Soranzo, Nicole; Stančáková, Alena; Steinhagen-Thiessen, Elisabeth; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Swart, Karin M.A.; Tan, Sian Tsung; Tarnopolsky, Mark A.; Thompson, Patricia; Thomson, Cynthia A.; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Tranah, Gregory J.; Tuomilehto, Jaakko; Van Schoor, Natasja M.; Verma, Arjun; Vollenweider, Peter; Völzke, Henry; Wactawski-Wende, Jean; Walker, Mark; Weedon, Michael N.; Welch, Ryan; Wichman, H. Erich; Widen, Elisabeth; Williams, Frances M.K.; Wilson, James F.; Wright, Nicole C.; Xie, Weijia; Yu, Lei; Zhou, Yanhua; Chambers, John C.; Döring, Angela; van Duijn, Cornelia M.; Econs, Michael J.; Gudnason, Vilmundur; Kooner, Jaspal S.; Psaty, Bruce M.; Spector, Timothy D.; Stefansson, Kari; Rivadeneira, Fernando; Uitterlinden, André G.; Wareham, Nicholas J.; Ossowski, Vicky; Waterworth, Dawn M.; Loos, Ruth J F; Karasik, David; Harris, Tamara B.; Ohlsson, Claes; Kiel, Douglas P.
In: Nature Communications, Vol. 8, No. 1, 80, 01.12.2017.Research output: Contribution to journal › Article › 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-Banjaw, 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 Vernon
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
AU - Bennett, David A.
AU - Bertram, Lars
AU - Biffar, Rainer
AU - Bochud, Murielle
AU - Boehnke, Michael
AU - Borecki, Ingrid B.
AU - Buchman, Aron S.
AU - Byberg, Liisa
AU - Campbell, Harry
AU - Campos Obanda, Natalia
AU - Cauley, Jane A.
AU - Cawthon, Peggy M.
AU - Cederberg, Henna
AU - Chen, Zhao
AU - Cho, Nam H.
AU - Jin Choi, Hyung
AU - Claussnitzer, Melina
AU - Collins, Francis S.
AU - Cummings, Steven R.
AU - De Jager, Philip L.
AU - Demuth, Ilja
AU - Dhonukshe-Rutten, Rosalie A.M.
AU - DIatchenko, Luda
AU - Eiriksdottir, Gudny
AU - Enneman, Anke W.
AU - Erdos, Mike
AU - Eriksson, Johan G.
AU - Eriksson, Joel
AU - Estrada, Karol
AU - Evans, Daniel S.
AU - Feitosa, Mary F.
AU - Fu, Mao
AU - Garcia, Melissa
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.
AU - Homuth, Georg
AU - Hsueh, Wen Chi
AU - Hubal, Monica J.
AU - Hubbard, Alan
AU - Huffman, Kim M.
AU - Husted, Lise Bjerre
AU - Illig, Thomas
AU - Ingelsson, Erik
AU - Ittermann, Till
AU - Jansson, John Olov
AU - Jordan, Joanne M.
AU - Jula, Antti
AU - Karlsson, Magnus
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
AU - Kuulasmaa, Teemu
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Lahti, Jari
AU - Lang, Thomas
AU - Langdahl, Bente Lomholt
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
AU - Luben, Robert N
AU - Maixner, William
AU - McGuigan, Fiona E.
AU - Medina-Gomez, Carolina
AU - Meitinger, Thomas
AU - Melhus, Håkan
AU - Mellström, Dan
AU - Melov, Simon
AU - Michaëlsson, Karl
AU - Mitchell, Braxton D.
AU - Morris, Andrew P.
AU - Mosekilde, Leif
AU - Newman, Anne
AU - Nielson, Carrie M.
AU - O'connell, Jeffrey R.
AU - Oostra, Ben A.
AU - Orwoll, Eric S.
AU - Palotie, Aarno
AU - Parker, Stephan
AU - Peacock, Munro
AU - Perola, Markus
AU - Peters, Annette
AU - Polasek, Ozren
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 J.
AU - Sehmi, Joban S.
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
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 M.
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 - 10.1038/s41467-017-00031-7
DO - 10.1038/s41467-017-00031-7
M3 - Article
C2 - 28724990
AN - SCOPUS:85025138148
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 80
ER -