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

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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 et al (show 183 more authors) , Kutalik, Zoltÿn, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Zhao, Jing Hua, Zhang, Weihua, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Ines, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Obanda, Natalia Campos, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Choi, Hyung Jin, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie AM, 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, Kilpainen, Tuomas O, Klopp, Norman, Kloth, Jacqueline SL, 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, Osten, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Hakan, Mellstrom, Dan, Melov, Simon, Michaelsson, 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, Raikkonen, 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, Shin, Chan Soo, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stancakova, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin MA, 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, Voelzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichman, H-Erich, Widen, Elisabeth, Williams, Frances MK, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Doring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, Andre G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth JF, Karasik, David, Harris, Tamara B, Ohlsson, Claes and Kiel, Douglas P (2017) Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. NATURE COMMUNICATIONS, 8 (1). 80-.

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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.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Item Type:	Article
Uncontrolled Keywords:	Humans, Thinness, 17-Hydroxysteroid Dehydrogenases, Aldehyde Oxidoreductases, Extracellular Matrix Proteins, Body Composition, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Versicans, Genome-Wide Association Study, Insulin Receptor Substrate Proteins, ADAMTS Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO
Depositing User:	Symplectic Admin
Date Deposited:	02 Aug 2017 15:38
Last Modified:	13 Oct 2023 00:00
DOI:	10.1038/s41467-017-00031-7
Open Access URL:	http://www.nature.com/articles/s41467-017-00031-7
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3008793