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

M.C. 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, J.A. 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 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 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.E. 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*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

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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.
    Original languageEnglish
    Article number80
    JournalNature Communications
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2017

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

      Zillikens, M. C., Demissie, S., Hsu, Y. H., Yerges-Armstrong, L. M., Chou, W. C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D. L., Kutalik, Z., Luan, J., Malkin, I., Ried, J. S., Smith, A. V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A. & 173 others, Åkesson, K., Amin, N., Baier, L. J., Barroso, I., Bennett, D. A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I. B., Buchman, A. S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J. A., Cawthon, P. M., Cederberg, H., Chen, Z., Cho, N. H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S. R., De Jager, P. L., Demuth, I., Dhonukshe-Rutten, R. A. M., Diatchenko, L., Eiriksdottir, G., Enneman, A. W., Erdos, M., Eriksson, J. G., Eriksson, J., Estrada, K., Evans, D. S., Feitosa, M. F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N. L., Grallert, H., Grewal, J., Han, B. G., Hanson, R. L., Hayward, C., Hofman, A., Hoffman, E. P., Homuth, G., Hsueh, W. C., Hubal, M. J., Hubbard, A., Huffman, K. M., Husted, L. B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J. O., Jordan, J. M., Jula, A., Karlsson, M., Khaw, K. T., Kilpeläinen, T. O., Klopp, N., Kloth, J. S. L., Koistinen, H. A., Kraus, W. E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B. L., Launer, L. J., Lee, J. Y., Lerch, M. M., Lewis, J. R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Liu, Y., Ljunggren, Ö., Lorentzon, M., Luben, R. N., Maixner, W., McGuigan, F. E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B. D., Morris, A. P., Mosekilde, L., Newman, A., Nielson, C. M., O'Connell, J. R., Oostra, B. A., Orwoll, E. S., Palotie, A., Parker, S. C. J., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R. L., Räikkönen, K., Ralston, S. H., Ripatti, S., Robbins, J. A., Rotter, J. I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E. E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E. A., Styrkarsdottir, U., Swart, K. M. A., Tan, S. T., Tarnopolsky, M. A., Thompson, P., Thomson, C. A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G. J., Tuomilehto, J., van Schoor, N. M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M. N., Welch, R., Wichmann, H. E., Widen, E., Williams, F. M. K., Wilson, J. F., Wright, N. C., Xie, W., Yu, L., Zhou, Y., Chambers, J. C., Döring, A., van Duijn, C. M., Econs, M. J., Gudnason, V., Kooner, J. S., Psaty, B. M., Spector, T. D., Stefansson, K., Rivadeneira, F., Uitterlinden, A. G., Wareham, N. J., Ossowski, V., Waterworth, D., Loos, R. J. F., Karasik, D., Harris, T. B., Ohlsson, C. & Kiel, D. P., 7 Nov 2017, In: Nature Communications. 8, 1, 1 p., 1414.

      Research output: Contribution to journalComment/Letter to the editorAcademic

      Open Access
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