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

M. Carola Zillikens, Serkalem Demissie, 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 V. Smith, Gudmar Thorleifsson, Liesbeth Vandenput, Jing Hua Zhao, Weihua Zhang, Ali AghdassiKristina 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 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 B. 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 L. Langdahl, Lenore J. Launer, Jong Young Lee, Markus M. Lerch, Joshua R. Lewis, Lars Lind, Cecilia 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 Scott, Joban 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 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 Waterworth, Ruth J.F. Loos, David Karasik, Tamara B. Harris, Claes Ohlsson, Douglas P. Kiel

Research output: Contribution to journalArticle

25 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 (US)
Article number80
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

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

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Zillikens, M. C., Demissie, 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

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. / Zillikens, M. Carola; Demissie, 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 V.; 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; 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 B.; 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 L.; Launer, Lenore J.; Lee, Jong Young; Lerch, Markus M.; Lewis, Joshua R.; Lind, Lars; Lindgren, Cecilia; 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; Sehmi, Joban; 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; 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; 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 journalArticle

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

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

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.

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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

UR - http://www.scopus.com/inward/citedby.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 -