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

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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 , Zhao , J H , Zhang , W , Aghdassi , A , Akesson , 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 , Obanda , N C , Cauley , J A , Cawthon , P M , Cederberg , H , Chen , Z , Cho , N H , Choi , H J , 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 , Kilpainen , 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 , O , Lorentzon , M , Luben , R N , Maixner , W , McGuigan , F E , Medina-Gomez , C , Meitinger , T , Melhus , H , Mellstrom , D , Melov , S , Michaelsson , 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 , Raikkonen , 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 , Shin , C S , Sigurdsson , G , Smith , S , Soranzo , N , Stancakova , 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 , Voelzke , 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 , Doring , 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 2017 , ' Large meta-analysis of genome-wide association studies identifies five loci for lean body mass ' , Nature Communications , vol. 8 , 80 . https://doi.org/10.1038/s41467-017-00031-7

Title: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
Author: 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, Zoltyn; 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 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; Kilpainen, 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, 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, Stephen C. J.; 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 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; Voelzke, Henry; Wactawski-Wende, Jean; Walker, Mark; Weedon, Michael N.; Welch, Ryan; Wichmann, H. -Erich; Widen, Elisabeth; Williams, Frances M. K.; 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 J. F.; Karasik, David; Harris, Tamara B.; Ohlsson, Claes; Kiel, Douglas P.
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, University of Helsinki
University of Helsinki, University of Helsinki
Date: 2017-07-19
Language: eng
Number of pages: 13
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/211420
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 x 10(-8)) or suggestively genome wide (p <2.3 x 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.
Subject: SKELETAL-MUSCLE MASS
BONE-MINERAL DENSITY
PHYSICAL-DISABILITY
INSULIN-RESISTANCE
GENE-EXPRESSION
UNITED-STATES
HUMAN HEIGHT
VARIANTS
OBESITY
SARCOPENIA
3121 General medicine, internal medicine and other clinical medicine
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