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 Aghdassi; Kristina 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 Kilpeläinen; 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 Räikkönen; 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 Wichmann; 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 Waterworth; Ruth J F Loos; David Karasik; Tamara B Harris; Claes Ohlsson; Douglas P Kiel

doi:10.1038/s41467-017-00031-7

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 Kilpeläinen, 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 Räikkönen, 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 Wichmann, 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 Waterworth, Ruth J F Loos, David Karasik, Tamara B Harris, Claes Ohlsson, Douglas P Kiel

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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.

Originalsprog	Engelsk
Artikelnummer	80
Tidsskrift	Nature Communications
Vol/bind	8
Antal sider	13
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-017-00031-7
Status	Udgivet - 1 dec. 2017

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10.1038/s41467-017-00031-7Licens: CC BY

s41467-017-00031-7Forlagets udgivne version, 360 KBLicens: CC BY

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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., Hua Zhao, J., Zhang, W., ... Kiel, D. P. (2017). Large meta-analysis of genome-wide association studies identifies five loci for lean body mass. Nature Communications, 8, [80]. https://doi.org/10.1038/s41467-017-00031-7

Zillikens, MC, Demissie, S, Hsu, Y-H, Yerges-Armstrong, LM, Chou, W-C, Stolk, L, Livshits, G, Broer, L, Johnson, T, Koller, DL, Kutalik, Z, Luan, J, 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, B-G, Hanson, RL, Hayward, C, Hofman, A, Hoffman, EP, Homuth, G, Hsueh, W-C, Hubal, MJ, Hubbard, A, Huffman, KM, Husted, LB, Illig, T, Ingelsson, E, Ittermann, T, Jansson, J-O, Jordan, JM, Jula, A, Karlsson, M, Khaw, K-T, Kilpeläinen, 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, J-Y, 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, Räikkönen, 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, S-T, 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, Wichmann, H-E, Widen, E, Williams, FMK, Wilson, JF, Wright, NC, Xie, W, Yu, L, Zhou, Y, Chambers, JC, Döring, A, van Duijn, CM, Econs, MJ, 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, bind 8, 80. https://doi.org/10.1038/s41467-017-00031-7

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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.",

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author = "Zillikens, {M Carola} and Serkalem Demissie and Yi-Hsiang Hsu and Yerges-Armstrong, {Laura M} and Wen-Chi Chou 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 Bok-Ghee Han and Hanson, {Robert L} and Caroline Hayward and Albert Hofman and Hoffman, {Eric P} and Georg Homuth and Wen-Chi Hsueh 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 John-Olov Jansson and Jordan, {Joanne M} and Antti Jula and Magnus Karlsson and Kay-Tee Khaw and Kilpel{\"a}inen, {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 Jong-Young Lee 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 R{\"a}ikk{\"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 Stan{\v c}{\'a}kov{\'a} and Elisabeth Steinhagen-Thiessen and Streeten, {Elizabeth A} and Unnur Styrkarsdottir and Swart, {Karin M A} and Sian-Tsung Tan 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 H-Erich Wichmann 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 Econs, {Michael J} 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}",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41467-017-00031-7",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

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

AU - Hayward, Caroline

AU - Hofman, Albert

AU - Hoffman, Eric P

AU - Homuth, Georg

AU - Hsueh, Wen-Chi

AU - Hubal, Monica J

AU - Hubbard, Alan

AU - Huffman, Kim M

AU - Husted, Lise B

AU - Illig, Thomas

AU - Ingelsson, Erik

AU - Ittermann, Till

AU - Jansson, John-Olov

AU - Jordan, Joanne M

AU - Jula, Antti

AU - Karlsson, Magnus

AU - Khaw, Kay-Tee

AU - Kilpeläinen, Tuomas O

AU - Klopp, Norman

AU - Kloth, Jacqueline S L

AU - Koistinen, Heikki A

AU - Kraus, William E

AU - Kritchevsky, Stephen

AU - Kuulasmaa, Teemu

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Lahti, Jari

AU - Lang, Thomas

AU - Langdahl, Bente L

AU - Launer, Lenore J

AU - Lee, Jong-Young

AU - Lerch, Markus M

AU - Lewis, Joshua R

AU - Lind, Lars

AU - Lindgren, Cecilia

AU - Liu, Yongmei

AU - Liu, Tian

AU - Liu, Youfang

AU - Ljunggren, Östen

AU - Lorentzon, Mattias

AU - Luben, Robert N

AU - Maixner, William

AU - McGuigan, Fiona E

AU - Medina-Gomez, Carolina

AU - Meitinger, Thomas

AU - Melhus, Håkan

AU - Mellström, Dan

AU - Melov, Simon

AU - Michaëlsson, Karl

AU - Mitchell, Braxton D

AU - Morris, Andrew P

AU - Mosekilde, Leif

AU - Newman, Anne

AU - Nielson, Carrie M

AU - O'Connell, Jeffrey R

AU - Oostra, Ben A

AU - Orwoll, Eric S

AU - Palotie, Aarno

AU - Parker, Stephan

AU - Peacock, Munro

AU - Perola, Markus

AU - Peters, Annette

AU - Polasek, Ozren

AU - Prince, Richard L

AU - Räikkönen, Katri

AU - Ralston, Stuart H

AU - Ripatti, Samuli

AU - Robbins, John A

AU - Rotter, Jerome I

AU - Rudan, Igor

AU - Salomaa, Veikko

AU - Satterfield, Suzanne

AU - Schadt, Eric E

AU - Schipf, Sabine

AU - Scott, Laura

AU - Sehmi, Joban

AU - Shen, Jian

AU - Soo Shin, Chan

AU - Sigurdsson, Gunnar

AU - Smith, Shad

AU - Soranzo, Nicole

AU - Stančáková, Alena

AU - Steinhagen-Thiessen, Elisabeth

AU - Streeten, Elizabeth A

AU - Styrkarsdottir, Unnur

AU - Swart, Karin M A

AU - Tan, Sian-Tsung

AU - Tarnopolsky, Mark A

AU - Thompson, Patricia

AU - Thomson, Cynthia A

AU - Thorsteinsdottir, Unnur

AU - Tikkanen, Emmi

AU - Tranah, Gregory J

AU - Tuomilehto, Jaakko

AU - van Schoor, Natasja M

AU - Verma, Arjun

AU - Vollenweider, Peter

AU - Völzke, Henry

AU - Wactawski-Wende, Jean

AU - Walker, Mark

AU - Weedon, Michael N

AU - Welch, Ryan

AU - Wichmann, H-Erich

AU - Widen, Elisabeth

AU - Williams, Frances M K

AU - Wilson, James F

AU - Wright, Nicole C

AU - Xie, Weijia

AU - Yu, Lei

AU - Zhou, Yanhua

AU - Chambers, John C

AU - Döring, Angela

AU - van Duijn, Cornelia M

AU - Econs, Michael J

AU - Gudnason, Vilmundur

AU - Kooner, Jaspal S

AU - Psaty, Bruce M

AU - Spector, Timothy D

AU - Stefansson, Kari

AU - Rivadeneira, Fernando

AU - Uitterlinden, André G

AU - Wareham, Nicholas J

AU - Ossowski, Vicky

AU - Waterworth, Dawn

AU - Loos, Ruth J F

AU - Karasik, David

AU - Harris, Tamara B

AU - Ohlsson, Claes

AU - Kiel, Douglas P

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.

KW - Journal Article

UR - https://www.nature.com/articles/s41467-017-01008-2

U2 - 10.1038/s41467-017-00031-7

DO - 10.1038/s41467-017-00031-7

M3 - Journal article

C2 - 28724990

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 80

ER -

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

Abstract

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