Disentangling the genetics of lean mass.

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.; Chen, Z.; Cho, N.H.; Choi, H.J.; Chou, W.C.; Cummings, S.R.; de Groot, LCPGM; De Jager, P.L.; Demuth, I.; Diatchenko, L.; Econs, M.J.; Eiriksdottir, G.; Enneman, A.W.; Eriksson, J.; Eriksson, J.G.; Estrada, K.; Evans, D.S.; Feitosa, M.F.; Fu, M.; Gieger, C.; Grallert, H.; Gudnason, V.; Lenore, L.J.; Hayward, C.; Hofman, A.; Homuth, G.; Huffman, K.M.; Husted, L.B.; Illig, T.; Ingelsson, E.; Ittermann, T.; Jansson, J.O.; Johnson, T.; Biffar, R.; Jordan, J.M.; Jula, A.; Karlsson, M.; Khaw, K.T.; Kilpeläinen, T.O.; Klopp, N.; Kloth, JSL; Koller, D.L.; Kooner, J.S.; Kraus, W.E.; Kritchevsky, S.; Kutalik, Z.; Kuulasmaa, T.; Kuusisto, J.; Laakso, M.; Lahti, J.; Lang, T.; Langdahl, B.L.; Lerch, M.M.; Lewis, J.R.; Lill, C.; Lind, L.; Lindgren, C.; Liu, Y.; Livshits, G.; Ljunggren, Ö.; Loos, RJF; Lorentzon, M.; Luan, J.; Luben, R.N.; Malkin, I.; McGuigan, F.E.; Medina-Gomez, C.; Meitinger, T.; Melhus, H.; Mellström, D.; Michaëlsson, K.; Mitchell, B.D.; Morris, A.P.; Mosekilde, L.; Nethander, M.; Newman, A.B.; O'Connell, J.R.; Oostra, B.A.; Orwoll, E.S.; Palotie, A.; Peacock, M.; Perola, M.; Peters, A.; Prince, R.L.; Psaty, B.M.; Räikkönen, K.; Ralston, S.H.; Ripatti, S.; Rivadeneira, F.; Robbins, J.A.; Rotter, J.I.; Rudan, I.; Salomaa, V.; Satterfield, S.; Schipf, S.; Shin, C.S.; Smith, A.V.; Smith, S.B.; Soranzo, N.; Spector, T.D.; Stancáková, A.; Stefansson, K.; Steinhagen-Thiessen, E.; Stolk, L.; Streeten, E.A.; Styrkarsdottir, U.; Swart, KMA; Thompson, P.; Thomson, C.A.; Thorleifsson, G.; Thorsteinsdottir, U.; Tikkanen, E.; Tranah, G.J.; Uitterlinden, A.G.; van Duijn, C.M.; van Schoor, N.M.; Vandenput, L.; Vollenweider, P.; Völzke, H.; Wactawski-Wende, J.; Walker, M.; J Wareham, N.; Waterworth, D.; Weedon, M.N.; Wichmann, H.E.; Widen, E.; Williams, FMK; Wilson, J.F.; Wright, N.C.; Yerges-Armstrong, L.M.; Yu, L.; Zhang, W.; Zhao, J.H.; Zhou, Y.; Nielson, C.M.; Harris, T.B.; Demissie, S.; Kiel, D.P.; Ohlsson, C.

doi:10.1093/ajcn/nqy272

Disentangling the genetics of lean mass.

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Serval ID

serval:BIB_180D03EFC038

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Disentangling the genetics of lean mass.

Journal

The American journal of clinical nutrition

Author(s)

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., Chen Z., Cho N.H., Choi H.J., Chou W.C., Cummings S.R., de Groot LCPGM, De Jager P.L., Demuth I., Diatchenko L., Econs M.J., Eiriksdottir G., Enneman A.W., Eriksson J., Eriksson J.G., Estrada K., Evans D.S., Feitosa M.F., Fu M., Gieger C., Grallert H., Gudnason V., Lenore L.J., Hayward C., Hofman A., Homuth G., Huffman K.M., Husted L.B., Illig T., Ingelsson E., Ittermann T., Jansson J.O., Johnson T., Biffar R., Jordan J.M., Jula A., Karlsson M., Khaw K.T., Kilpeläinen T.O., Klopp N., Kloth JSL, Koller D.L., Kooner J.S., Kraus W.E., Kritchevsky S., Kutalik Z., Kuulasmaa T., Kuusisto J., Laakso M., Lahti J., Lang T., Langdahl B.L., Lerch M.M., Lewis J.R., Lill C., Lind L., Lindgren C., Liu Y., Livshits G., Ljunggren Ö., Loos RJF, Lorentzon M., Luan J., Luben R.N., Malkin I., McGuigan F.E., Medina-Gomez C., Meitinger T., Melhus H., Mellström D., Michaëlsson K., Mitchell B.D., Morris A.P., Mosekilde L., Nethander M., Newman A.B., O'Connell J.R., Oostra B.A., Orwoll E.S., Palotie A., Peacock M., Perola M., Peters A., Prince R.L., Psaty B.M., Räikkönen K., Ralston S.H., Ripatti S., Rivadeneira F., Robbins J.A., Rotter J.I., Rudan I., Salomaa V., Satterfield S., Schipf S., Shin C.S., Smith A.V., Smith S.B., Soranzo N., Spector T.D., Stancáková A., Stefansson K., Steinhagen-Thiessen E., Stolk L., Streeten E.A., Styrkarsdottir U., Swart KMA, Thompson P., Thomson C.A., Thorleifsson G., Thorsteinsdottir U., Tikkanen E., Tranah G.J., Uitterlinden A.G., van Duijn C.M., van Schoor N.M., Vandenput L., Vollenweider P., Völzke H., Wactawski-Wende J., Walker M., J Wareham N., Waterworth D., Weedon M.N., Wichmann H.E., Widen E., Williams FMK, Wilson J.F., Wright N.C., Yerges-Armstrong L.M., Yu L., Zhang W., Zhao J.H., Zhou Y., Nielson C.M., Harris T.B., Demissie S., Kiel D.P., Ohlsson C.

ISSN

1938-3207 (Electronic)

ISSN-L

0002-9165

Publication state

Published

Issued date

01/02/2019

Peer-reviewed

Oui

Volume

109

Number

Pages

276-287

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

Abstract

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.
To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci.
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).
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.
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.

Keywords

ADAMTS Proteins/genetics, Absorptiometry, Photon, Adipose Tissue/metabolism, Adolescent, Adult, Aged, Aged, 80 and over, Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics, Body Composition/genetics, Body Fluid Compartments/metabolism, Electric Impedance, European Continental Ancestry Group/genetics, Extracellular Matrix Proteins/genetics, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Muscle, Skeletal/metabolism, Phenotype, Polymorphism, Single Nucleotide, RNA-Binding Proteins/genetics, Receptor, Melanocortin, Type 4/genetics, Versicans/genetics, Young Adult

OAI-PMH

oai:serval.unil.ch:BIB_180D03EFC038

DOI

10.1093/ajcn/nqy272

Pubmed

30721968

Web of science

000460615600007

Create date

15/02/2019 15:26

Last modification date

31/10/2019 15:32

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Disentangling the genetics of lean mass.

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