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

Authors :
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
Kilpeläinen, 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
Räikkönen, 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
Wichmann, 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
Loos, Ruth J F
Karasik, David
Harris, Tamara B
Ohlsson, Claes
Kiel, Douglas P
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
Kilpeläinen, 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
Räikkönen, 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
Wichmann, 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
Loos, Ruth J F
Karasik, David
Harris, Tamara B
Ohlsson, Claes
Kiel, Douglas P
Source :
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 , 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 , 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
Publication Year :
2017

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.

Details

Database :
OAIster
Journal :
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 , 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 , 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
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322700006
Document Type :
Electronic Resource