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

M. Carola Zillikens, Serkalem Demissie-Banjaw, Yi-Hsiang Hsu, Laura M. Yerges-Armstrong, Wen Chi Chou, Lisette Stolk, Gregory Livshits, Linda Broer, Toby Johnson, Daniel L. Koller, Zoltán Kutalik, Jian'An Luan, Ida Malkin, Janina S. Ried, Albert Vernon Smith, Gudmar Thorleifsson, Liesbeth Vandenput, Jing Hua Zhao, Weihua Zhang, Ali Aghdassi & 173 others Kristina Åkesson, Najaf Amin, Leslie J. Baier, Inês Barroso, David A. Bennett, Lars Bertram, Rainer Biffar, Murielle Bochud, Michael Boehnke, Ingrid B. Borecki, Aron S. Buchman, Liisa Byberg, Harry Campbell, Natalia Campos Obanda, Jane A. Cauley, Peggy M. Cawthon, Henna Cederberg, Zhao Chen, Nam H. Cho, Hyung Jin Choi, Melina Claussnitzer, Francis S. Collins, Steven R. Cummings, Philip L. De Jager, Ilja Demuth, Rosalie A.M. Dhonukshe-Rutten, Luda DIatchenko, Gudny Eiriksdottir, Anke W. Enneman, Mike Erdos, Johan G. Eriksson, Joel Eriksson, Karol Estrada, Daniel S. Evans, Mary F. Feitosa, Mao Fu, Melissa Garcia, Christian Gieger, Thomas Girke, Nicole L. Glazer, Harald Grallert, Jagvir Grewal, Bok Ghee Han, Robert L. Hanson, Caroline Hayward, Albert Hofman, Eric P. Hoffman, Georg Homuth, Wen Chi Hsueh, Monica J. Hubal, Alan Hubbard, Kim M. Huffman, Lise Bjerre Husted, Thomas Illig, Erik Ingelsson, Till Ittermann, John Olov Jansson, Joanne M. Jordan, Antti Jula, Magnus Karlsson, Kay Tee Khaw, Tuomas O. Kilpelaïnen, Norman Klopp, Jacqueline S.L. Kloth, Heikki A. Koistinen, William E. Kraus, Stephen Kritchevsky, Teemu Kuulasmaa, Johanna Kuusisto, Markku Laakso, Jari Lahti, Thomas Lang, Bente Lomholt Langdahl, Lenore J. Launer, Jong Young Lee, Markus M. Lerch, Joshua R. Lewis, Lars Lind, Cecilia M. Lindgren, Yongmei Liu, Tian Liu, Youfang Liu, Östen Ljunggren, Mattias Lorentzon, Robert N Luben, William Maixner, Fiona E. McGuigan, Carolina Medina-Gomez, Thomas Meitinger, Håkan Melhus, Dan Mellström, Simon Melov, Karl Michaëlsson, Braxton D. Mitchell, Andrew P. Morris, Leif Mosekilde, Anne Newman, Carrie M. Nielson, Jeffrey R. O'connell, Ben A. Oostra, Eric S. Orwoll, Aarno Palotie, Stephan Parker, Munro Peacock, Markus Perola, Annette Peters, Ozren Polasek, Richard L. Prince, Katri Raïkkönen, Stuart H. Ralston, Samuli Ripatti, John A. Robbins, Jerome I. Rotter, Igor Rudan, Veikko Salomaa, Suzanne Satterfield, Eric E. Schadt, Sabine Schipf, Laura J. Scott, Joban S. Sehmi, Jian Shen, Chan Soo Shin, Gunnar Sigurdsson, Shad Smith, Nicole Soranzo, Alena Stančáková, Elisabeth Steinhagen-Thiessen, Elizabeth A. Streeten, Unnur Styrkarsdottir, Karin M.A. Swart, Sian Tsung Tan, Mark A. Tarnopolsky, Patricia Thompson, Cynthia A. Thomson, Unnur Thorsteinsdottir, Emmi Tikkanen, Gregory J. Tranah, Jaakko Tuomilehto, Natasja M. Van Schoor, Arjun Verma, Peter Vollenweider, Henry Völzke, Jean Wactawski-Wende, Mark Walker, Michael N. Weedon, Ryan Welch, H. Erich Wichman, Elisabeth Widen, Frances M.K. Williams, James F. Wilson, Nicole C. Wright, Weijia Xie, Lei Yu, Yanhua Zhou, John C. Chambers, Angela Döring, Cornelia M. van Duijn, Michael J. Econs, Vilmundur Gudnason, Jaspal S. Kooner, Bruce M. Psaty, Timothy D. Spector, Kari Stefansson, Fernando Rivadeneira, André G. Uitterlinden, Nicholas J. Wareham, Vicky Ossowski, Dawn M. Waterworth, Ruth J F Loos, David Karasik, Tamara B. Harris, Claes Ohlsson, Douglas P. Kiel

Research output: Contribution to journal › Article

29 Citations (Scopus)

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 languageEnglish
Article number80
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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genome
Genome-Wide Association Study
loci
Polymorphism
Single Nucleotide Polymorphism
Meta-Analysis
Nucleotides
Genes
Genome
Acoustic impedance
Photon Absorptiometry
Electric Impedance
polymorphism
nucleotides
Muscle
Leg
Skeletal Muscle
Arm
Aging of materials
Fats

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Zillikens, M. C., Demissie-Banjaw, S., Hsu, Y-H., Yerges-Armstrong, L. M., Chou, W. C., Stolk, L., ... Kiel, D. P. (2017). Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nature Communications, 8(1), [80]. https://doi.org/10.1038/s41467-017-00031-7
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. / Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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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.",
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Zillikens, MC, Demissie-Banjaw, S, Hsu, Y-H, Yerges-Armstrong, LM, Chou, WC, Stolk, L, Livshits, G, Broer, L, Johnson, T, Koller, DL, Kutalik, Z, Luan, JA, 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, FS, 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, Kilpelaïnen, 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, CM, 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, S, Peacock, M, Perola, M, Peters, A, Polasek, O, Prince, RL, Raïkkönen, K, Ralston, SH, Ripatti, S, Robbins, JA, Rotter, JI, Rudan, I, Salomaa, V, Satterfield, S, Schadt, EE, Schipf, S, Scott, LJ, Sehmi, JS, 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, Wichman, 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, DM, Loos, RJF, Karasik, D, Harris, TB, Ohlsson, C & Kiel, DP 2017, 'Large meta-analysis of genome-wide association studies identifies five loci for lean body mass' Nature Communications, vol. 8, no. 1, 80. https://doi.org/10.1038/s41467-017-00031-7

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

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

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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

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 80

ER -

Zillikens MC, Demissie-Banjaw S, Hsu Y-H, Yerges-Armstrong LM, Chou WC, Stolk L et al. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nature Communications. 2017 Dec 1;8(1). 80. https://doi.org/10.1038/s41467-017-00031-7

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