Standard
Disentangling the genetics of lean mass. / Karasik, David; Zillikens, M. Carola; Hsu, Yi Hsiang; Aghdassi, Ali; Akesson, Kristina; Amin, Najaf; Barroso, Inês; Bennett, David A.; Bertram, Lars; Bochud, Murielle; Borecki, Ingrid B.; Broer, Linda; Buchman, Aron S.; Byberg, Liisa; Campbell, Harry; Campos-Obando, Natalia; Cauley, Jane A.; Cawthon, Peggy M.; Chambers, John C.; Chen, Zhao; Cho, Nam H.; Choi, Hyung Jin; Chou, Wen Chi; Cummings, Steven R.; de Groot, Lisette C.P.G.M.; De Jager, Phillip L.; Demuth, Ilja; Diatchenko, Luda; Econs, Michael J.; Eiriksdottir, Gudny; Enneman, Anke W.; Eriksson, Joel; Eriksson, Johan G.; Estrada, Karol; Evans, Daniel S.; Feitosa, Mary F.; Fu, Mao; Gieger, Christian; Grallert, Harald; Gudnason, Vilmundur; Lenore, Launer J.; Hayward, Caroline; Hofman, Albert; Homuth, Georg; Huffman, Kim M.; Husted, Lise B.; Illig, Thomas; Ingelsson, Erik; Ittermann, Till; Jansson, John Olov; Johnson, Toby; Biffar, Reiner; Jordan, Joanne M.; Jula, Antti; Karlsson, Magnus; Khaw, Kay Tee; Kilpeläinen, Tuomas O.; Klopp, Norman; Kloth, Jacqueline S.L.; Koller, Daniel L.; Kooner, Jaspal S.; Kraus, William E.; Kritchevsky, Stephen; Kutalik, Zoltán; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku; Lahti, Jari; Lang, Thomas; Langdahl, Bente L.; Lerch, Markus M.; Lewis, Joshua R.; Lill, Christina; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Livshits, Gregory; Ljunggren, Östen; Loos, Ruth J.F.; Lorentzon, Mattias; Luan, Jian'an; Luben, Robert N.; Malkin, Ida; McGuigan, Fiona E.; Medina-Gomez, Carolina; Meitinger, Thomas; Melhus, Håkan; Mellström, Dan; Michaëlsson, Karl; Mitchell, Braxton D.; Morris, Andrew P.; Mosekilde, Leif; Nethander, Maria; Newman, Anne B.; O'Connell, Jeffery R.; Oostra, Ben A.; Orwoll, Eric S.; Palotie, Aarno; Peacock, Munro; Perola, Markus; Peters, Annette; Prince, Richard L.; Psaty, Bruce M.; Räikkönen, Katri; Ralston, Stuart H.; Ripatti, Samuli; Rivadeneira, Fernando; Robbins, John A.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Satterfield, Suzanne; Schipf, Sabine; Shin, Chan Soo; Smith, Albert V.; Smith, Shad B.; Soranzo, Nicole; Spector, Timothy D.; Stancáková, Alena; Stefansson, Kari; Steinhagen-Thiessen, Elisabeth; Stolk, Lisette; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Swart, Karin M.A.; Thompson, Patricia; Thomson, Cynthia A.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Tranah, Gregory J.; Uitterlinden, André G.; van Duijn, Cornelia M.; van Schoor, Natasja M.; Vandenput, Liesbeth; Vollenweider, Peter; Völzke, Henry; Wactawski-Wende, Jean; Walker, Mark; J Wareham, Nicholas; Waterworth, Dawn; Weedon, Michael N.; Wichmann, H. Erich; Widen, Elisabeth; Williams, Frances M.K.; Wilson, James F.; Wright, Nicole C.; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Zhou, Yanhua; Nielson, Carrie M.; Harris, Tamara B.; Demissie, Serkalem; Kiel, Douglas P.; Ohlsson, Claes.
In:
American Journal of Clinical Nutrition, Vol. 109, No. 2, 2019, p. 276-287.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Karasik, D, Zillikens, MC, Hsu, YH, Aghdassi, A, Akesson, K, Amin, N, Barroso, I, Bennett, DA, Bertram, L, Bochud, M, Borecki, IB, Broer, L, Buchman, AS, Byberg, L, Campbell, H, Campos-Obando, N, Cauley, JA, Cawthon, PM, Chambers, JC, Chen, Z, Cho, NH, Choi, HJ, Chou, WC, Cummings, SR, de Groot, LCPGM, De Jager, PL, Demuth, I, Diatchenko, L, Econs, MJ, Eiriksdottir, G, Enneman, AW, Eriksson, J, Eriksson, JG, Estrada, K, Evans, DS, Feitosa, MF, Fu, M, Gieger, C, Grallert, H, Gudnason, V, Lenore, LJ, Hayward, C, Hofman, A, Homuth, G, Huffman, KM, Husted, LB, Illig, T, Ingelsson, E, Ittermann, T, Jansson, JO, Johnson, T, Biffar, R, Jordan, JM, Jula, A, Karlsson, M, Khaw, KT
, Kilpeläinen, TO, Klopp, N, Kloth, JSL, Koller, DL, Kooner, JS, Kraus, WE, Kritchevsky, S, Kutalik, Z, Kuulasmaa, T, Kuusisto, J, Laakso, M, Lahti, J, Lang, T, Langdahl, BL, Lerch, MM, Lewis, JR, Lill, C, Lind, L, Lindgren, C, Liu, Y, Livshits, G, Ljunggren, Ö
, Loos, RJF, Lorentzon, M, Luan, J, Luben, RN, Malkin, I, McGuigan, FE, Medina-Gomez, C, Meitinger, T, Melhus, H, Mellström, D, Michaëlsson, K, Mitchell, BD, Morris, AP, Mosekilde, L, Nethander, M, Newman, AB, O'Connell, JR, Oostra, BA, Orwoll, ES, Palotie, A, Peacock, M, Perola, M, Peters, A, Prince, RL, Psaty, BM, Räikkönen, K, Ralston, SH, Ripatti, S, Rivadeneira, F, Robbins, JA, Rotter, JI, Rudan, I, Salomaa, V, Satterfield, S, Schipf, S, Shin, CS, Smith, AV, Smith, SB, Soranzo, N, Spector, TD, Stancáková, A, Stefansson, K, Steinhagen-Thiessen, E, Stolk, L, Streeten, EA, Styrkarsdottir, U, Swart, KMA, Thompson, P, Thomson, CA, Thorleifsson, G, Thorsteinsdottir, U, Tikkanen, E, Tranah, GJ, Uitterlinden, AG, van Duijn, CM, van Schoor, NM, Vandenput, L, Vollenweider, P, Völzke, H, Wactawski-Wende, J, Walker, M, J Wareham, N, Waterworth, D, Weedon, MN, Wichmann, HE, Widen, E, Williams, FMK, Wilson, JF, Wright, NC, Yerges-Armstrong, LM, Yu, L, Zhang, W, Zhao, JH, Zhou, Y, Nielson, CM, Harris, TB, Demissie, S, Kiel, DP & Ohlsson, C 2019, '
Disentangling the genetics of lean mass',
American Journal of Clinical Nutrition, vol. 109, no. 2, pp. 276-287.
https://doi.org/10.1093/ajcn/nqy272APA
Karasik, D., Zillikens, M. C., Hsu, Y. H., Aghdassi, A., Akesson, K., Amin, N., Barroso, I., Bennett, D. A., Bertram, L., Bochud, M., Borecki, I. B., Broer, L., Buchman, A. S., Byberg, L., Campbell, H., Campos-Obando, N., Cauley, J. A., Cawthon, P. M., Chambers, J. C., ... Ohlsson, C. (2019).
Disentangling the genetics of lean mass.
American Journal of Clinical Nutrition,
109(2), 276-287.
https://doi.org/10.1093/ajcn/nqy272Vancouver
Karasik D, Zillikens MC, Hsu YH, Aghdassi A, Akesson K, Amin N et al.
Disentangling the genetics of lean mass.
American Journal of Clinical Nutrition. 2019;109(2):276-287.
https://doi.org/10.1093/ajcn/nqy272Author
Karasik, David ; Zillikens, M. Carola ; Hsu, Yi Hsiang ; Aghdassi, Ali ; Akesson, Kristina ; Amin, Najaf ; Barroso, Inês ; Bennett, David A. ; Bertram, Lars ; Bochud, Murielle ; Borecki, Ingrid B. ; Broer, Linda ; Buchman, Aron S. ; Byberg, Liisa ; Campbell, Harry ; Campos-Obando, Natalia ; Cauley, Jane A. ; Cawthon, Peggy M. ; Chambers, John C. ; Chen, Zhao ; Cho, Nam H. ; Choi, Hyung Jin ; Chou, Wen Chi ; Cummings, Steven R. ; de Groot, Lisette C.P.G.M. ; De Jager, Phillip L. ; Demuth, Ilja ; Diatchenko, Luda ; Econs, Michael J. ; Eiriksdottir, Gudny ; Enneman, Anke W. ; Eriksson, Joel ; Eriksson, Johan G. ; Estrada, Karol ; Evans, Daniel S. ; Feitosa, Mary F. ; Fu, Mao ; Gieger, Christian ; Grallert, Harald ; Gudnason, Vilmundur ; Lenore, Launer J. ; Hayward, Caroline ; Hofman, Albert ; Homuth, Georg ; Huffman, Kim M. ; Husted, Lise B. ; Illig, Thomas ; Ingelsson, Erik ; Ittermann, Till ; Jansson, John Olov ; Johnson, Toby ; Biffar, Reiner ; Jordan, Joanne M. ; Jula, Antti ; Karlsson, Magnus ; Khaw, Kay Tee ; Kilpeläinen, Tuomas O. ; Klopp, Norman ; Kloth, Jacqueline S.L. ; Koller, Daniel L. ; Kooner, Jaspal S. ; Kraus, William E. ; Kritchevsky, Stephen ; Kutalik, Zoltán ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Laakso, Markku ; Lahti, Jari ; Lang, Thomas ; Langdahl, Bente L. ; Lerch, Markus M. ; Lewis, Joshua R. ; Lill, Christina ; Lind, Lars ; Lindgren, Cecilia ; Liu, Yongmei ; Livshits, Gregory ; Ljunggren, Östen ; Loos, Ruth J.F. ; Lorentzon, Mattias ; Luan, Jian'an ; Luben, Robert N. ; Malkin, Ida ; McGuigan, Fiona E. ; Medina-Gomez, Carolina ; Meitinger, Thomas ; Melhus, Håkan ; Mellström, Dan ; Michaëlsson, Karl ; Mitchell, Braxton D. ; Morris, Andrew P. ; Mosekilde, Leif ; Nethander, Maria ; Newman, Anne B. ; O'Connell, Jeffery R. ; Oostra, Ben A. ; Orwoll, Eric S. ; Palotie, Aarno ; Peacock, Munro ; Perola, Markus ; Peters, Annette ; Prince, Richard L. ; Psaty, Bruce M. ; Räikkönen, Katri ; Ralston, Stuart H. ; Ripatti, Samuli ; Rivadeneira, Fernando ; Robbins, John A. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Satterfield, Suzanne ; Schipf, Sabine ; Shin, Chan Soo ; Smith, Albert V. ; Smith, Shad B. ; Soranzo, Nicole ; Spector, Timothy D. ; Stancáková, Alena ; Stefansson, Kari ; Steinhagen-Thiessen, Elisabeth ; Stolk, Lisette ; Streeten, Elizabeth A. ; Styrkarsdottir, Unnur ; Swart, Karin M.A. ; Thompson, Patricia ; Thomson, Cynthia A. ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Tikkanen, Emmi ; Tranah, Gregory J. ; Uitterlinden, André G. ; van Duijn, Cornelia M. ; van Schoor, Natasja M. ; Vandenput, Liesbeth ; Vollenweider, Peter ; Völzke, Henry ; Wactawski-Wende, Jean ; Walker, Mark ; J Wareham, Nicholas ; Waterworth, Dawn ; Weedon, Michael N. ; Wichmann, H. Erich ; Widen, Elisabeth ; Williams, Frances M.K. ; Wilson, James F. ; Wright, Nicole C. ; Yerges-Armstrong, Laura M. ; Yu, Lei ; Zhang, Weihua ; Zhao, Jing Hua ; Zhou, Yanhua ; Nielson, Carrie M. ; Harris, Tamara B. ; Demissie, Serkalem ; Kiel, Douglas P. ; Ohlsson, Claes. / Disentangling the genetics of lean mass. In: American Journal of Clinical Nutrition. 2019 ; Vol. 109, No. 2. pp. 276-287.
Bibtex
@article{f2e0b652780b4c7d84013f24092cb6bc,
title = "Disentangling the genetics of lean mass",
abstract = "Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as {"}sumo wrestler{"} loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed {"}body builder{"} loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in {"}body builder{"} loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.",
author = "David Karasik and Zillikens, {M. Carola} and Hsu, {Yi Hsiang} and Ali Aghdassi and Kristina Akesson and Najaf Amin and In{\^e}s Barroso and Bennett, {David A.} and Lars Bertram and Murielle Bochud and Borecki, {Ingrid B.} and Linda Broer and Buchman, {Aron S.} and Liisa Byberg and Harry Campbell and Natalia Campos-Obando and Cauley, {Jane A.} and Cawthon, {Peggy M.} and Chambers, {John C.} and Zhao Chen and Cho, {Nam H.} and Choi, {Hyung Jin} and Chou, {Wen Chi} and Cummings, {Steven R.} and {de Groot}, {Lisette C.P.G.M.} and {De Jager}, {Phillip L.} and Ilja Demuth and Luda Diatchenko and Econs, {Michael J.} and Gudny Eiriksdottir and Enneman, {Anke W.} and Joel Eriksson and Eriksson, {Johan G.} and Karol Estrada and Evans, {Daniel S.} and Feitosa, {Mary F.} and Mao Fu and Christian Gieger and Harald Grallert and Vilmundur Gudnason and Lenore, {Launer J.} and Caroline Hayward and Albert Hofman and Georg Homuth and Huffman, {Kim M.} and Husted, {Lise B.} and Thomas Illig and Erik Ingelsson and Till Ittermann and Jansson, {John Olov} and Toby Johnson and Reiner Biffar and Jordan, {Joanne M.} and Antti Jula and Magnus Karlsson and Khaw, {Kay Tee} and Kilpel{\"a}inen, {Tuomas O.} and Norman Klopp and Kloth, {Jacqueline S.L.} and Koller, {Daniel L.} and Kooner, {Jaspal S.} and Kraus, {William E.} and Stephen Kritchevsky and Zolt{\'a}n Kutalik and Teemu Kuulasmaa and Johanna Kuusisto and Markku Laakso and Jari Lahti and Thomas Lang and Langdahl, {Bente L.} and Lerch, {Markus M.} and Lewis, {Joshua R.} and Christina Lill and Lars Lind and Cecilia Lindgren and Yongmei Liu and Gregory Livshits and {\"O}sten Ljunggren and Loos, {Ruth J.F.} and Mattias Lorentzon and Jian'an Luan and Luben, {Robert N.} and Ida Malkin and McGuigan, {Fiona E.} and Carolina Medina-Gomez and Thomas Meitinger and H{\aa}kan Melhus and Dan Mellstr{\"o}m and Karl Micha{\"e}lsson and Mitchell, {Braxton D.} and Morris, {Andrew P.} and Leif Mosekilde and Maria Nethander and Newman, {Anne B.} and O'Connell, {Jeffery R.} and Oostra, {Ben A.} and Orwoll, {Eric S.} and Aarno Palotie and Munro Peacock and Markus Perola and Annette Peters and Prince, {Richard L.} and Psaty, {Bruce M.} and Katri R{\"a}ikk{\"o}nen and Ralston, {Stuart H.} and Samuli Ripatti and Fernando Rivadeneira and Robbins, {John A.} and Rotter, {Jerome I.} and Igor Rudan and Veikko Salomaa and Suzanne Satterfield and Sabine Schipf and Shin, {Chan Soo} and Smith, {Albert V.} and Smith, {Shad B.} and Nicole Soranzo and Spector, {Timothy D.} and Alena Stanc{\'a}kov{\'a} and Kari Stefansson and Elisabeth Steinhagen-Thiessen and Lisette Stolk and Streeten, {Elizabeth A.} and Unnur Styrkarsdottir and Swart, {Karin M.A.} and Patricia Thompson and Thomson, {Cynthia A.} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Emmi Tikkanen and Tranah, {Gregory J.} and Uitterlinden, {Andr{\'e} G.} and {van Duijn}, {Cornelia M.} and {van Schoor}, {Natasja M.} and Liesbeth Vandenput and Peter Vollenweider and Henry V{\"o}lzke and Jean Wactawski-Wende and Mark Walker and {J Wareham}, Nicholas and Dawn Waterworth and Weedon, {Michael N.} and Wichmann, {H. Erich} and Elisabeth Widen and Williams, {Frances M.K.} and Wilson, {James F.} and Wright, {Nicole C.} and Yerges-Armstrong, {Laura M.} and Lei Yu and Weihua Zhang and Zhao, {Jing Hua} and Yanhua Zhou and Nielson, {Carrie M.} and Harris, {Tamara B.} and Serkalem Demissie and Kiel, {Douglas P.} and Claes Ohlsson",
year = "2019",
doi = "10.1093/ajcn/nqy272",
language = "English",
volume = "109",
pages = "276--287",
journal = "American Journal of Clinical Nutrition",
issn = "0002-9165",
publisher = "American Society for Nutrition",
number = "2",
}
RIS
TY - JOUR
T1 - Disentangling the genetics of lean mass
AU - Karasik, David
AU - Zillikens, M. Carola
AU - Hsu, Yi Hsiang
AU - Aghdassi, Ali
AU - Akesson, Kristina
AU - Amin, Najaf
AU - Barroso, Inês
AU - Bennett, David A.
AU - Bertram, Lars
AU - Bochud, Murielle
AU - Borecki, Ingrid B.
AU - Broer, Linda
AU - Buchman, Aron S.
AU - Byberg, Liisa
AU - Campbell, Harry
AU - Campos-Obando, Natalia
AU - Cauley, Jane A.
AU - Cawthon, Peggy M.
AU - Chambers, John C.
AU - Chen, Zhao
AU - Cho, Nam H.
AU - Choi, Hyung Jin
AU - Chou, Wen Chi
AU - Cummings, Steven R.
AU - de Groot, Lisette C.P.G.M.
AU - De Jager, Phillip L.
AU - Demuth, Ilja
AU - Diatchenko, Luda
AU - Econs, Michael J.
AU - Eiriksdottir, Gudny
AU - Enneman, Anke W.
AU - Eriksson, Joel
AU - Eriksson, Johan G.
AU - Estrada, Karol
AU - Evans, Daniel S.
AU - Feitosa, Mary F.
AU - Fu, Mao
AU - Gieger, Christian
AU - Grallert, Harald
AU - Gudnason, Vilmundur
AU - Lenore, Launer J.
AU - Hayward, Caroline
AU - Hofman, Albert
AU - Homuth, Georg
AU - Huffman, Kim M.
AU - Husted, Lise B.
AU - Illig, Thomas
AU - Ingelsson, Erik
AU - Ittermann, Till
AU - Jansson, John Olov
AU - Johnson, Toby
AU - Biffar, Reiner
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 - Koller, Daniel L.
AU - Kooner, Jaspal S.
AU - Kraus, William E.
AU - Kritchevsky, Stephen
AU - Kutalik, Zoltán
AU - Kuulasmaa, Teemu
AU - Kuusisto, Johanna
AU - Laakso, Markku
AU - Lahti, Jari
AU - Lang, Thomas
AU - Langdahl, Bente L.
AU - Lerch, Markus M.
AU - Lewis, Joshua R.
AU - Lill, Christina
AU - Lind, Lars
AU - Lindgren, Cecilia
AU - Liu, Yongmei
AU - Livshits, Gregory
AU - Ljunggren, Östen
AU - Loos, Ruth J.F.
AU - Lorentzon, Mattias
AU - Luan, Jian'an
AU - Luben, Robert N.
AU - Malkin, Ida
AU - McGuigan, Fiona E.
AU - Medina-Gomez, Carolina
AU - Meitinger, Thomas
AU - Melhus, Håkan
AU - Mellström, Dan
AU - Michaëlsson, Karl
AU - Mitchell, Braxton D.
AU - Morris, Andrew P.
AU - Mosekilde, Leif
AU - Nethander, Maria
AU - Newman, Anne B.
AU - O'Connell, Jeffery R.
AU - Oostra, Ben A.
AU - Orwoll, Eric S.
AU - Palotie, Aarno
AU - Peacock, Munro
AU - Perola, Markus
AU - Peters, Annette
AU - Prince, Richard L.
AU - Psaty, Bruce M.
AU - Räikkönen, Katri
AU - Ralston, Stuart H.
AU - Ripatti, Samuli
AU - Rivadeneira, Fernando
AU - Robbins, John A.
AU - Rotter, Jerome I.
AU - Rudan, Igor
AU - Salomaa, Veikko
AU - Satterfield, Suzanne
AU - Schipf, Sabine
AU - Shin, Chan Soo
AU - Smith, Albert V.
AU - Smith, Shad B.
AU - Soranzo, Nicole
AU - Spector, Timothy D.
AU - Stancáková, Alena
AU - Stefansson, Kari
AU - Steinhagen-Thiessen, Elisabeth
AU - Stolk, Lisette
AU - Streeten, Elizabeth A.
AU - Styrkarsdottir, Unnur
AU - Swart, Karin M.A.
AU - Thompson, Patricia
AU - Thomson, Cynthia A.
AU - Thorleifsson, Gudmar
AU - Thorsteinsdottir, Unnur
AU - Tikkanen, Emmi
AU - Tranah, Gregory J.
AU - Uitterlinden, André G.
AU - van Duijn, Cornelia M.
AU - van Schoor, Natasja M.
AU - Vandenput, Liesbeth
AU - Vollenweider, Peter
AU - Völzke, Henry
AU - Wactawski-Wende, Jean
AU - Walker, Mark
AU - J Wareham, Nicholas
AU - Waterworth, Dawn
AU - Weedon, Michael N.
AU - Wichmann, H. Erich
AU - Widen, Elisabeth
AU - Williams, Frances M.K.
AU - Wilson, James F.
AU - Wright, Nicole C.
AU - Yerges-Armstrong, Laura M.
AU - Yu, Lei
AU - Zhang, Weihua
AU - Zhao, Jing Hua
AU - Zhou, Yanhua
AU - Nielson, Carrie M.
AU - Harris, Tamara B.
AU - Demissie, Serkalem
AU - Kiel, Douglas P.
AU - Ohlsson, Claes
PY - 2019
Y1 - 2019
N2 - Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
AB - Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.
U2 - 10.1093/ajcn/nqy272
DO - 10.1093/ajcn/nqy272
M3 - Journal article
C2 - 30721968
AN - SCOPUS:85061513446
VL - 109
SP - 276
EP - 287
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 2
ER -
