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Disentangling the genetics of lean mass
Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Bar Ilan Univ, Azrieli Fac Med, Safed, Israel.
Erasmus MC, Dept Internal Med, Rotterdam, Netherlands;Netherlands Genom Initiat, Leiden, Netherlands.
Hebrew Senior Life Inst Aging Res, Boston, MA USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA 02115 USA;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA USA.
Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany.
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2019 (English)In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 109, no 2, p. 276-287Article in journal (Refereed) Published
Abstract [en]

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, age(2), 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 LMwere 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.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 109, no 2, p. 276-287
Keywords [en]
body composition, skeletal muscle, body fat, meta-analysis of genome-wide association studies, metabolic profile
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:uu:diva-380499DOI: 10.1093/ajcn/nqy272ISI: 000460615600007PubMedID: 30721968OAI: oai:DiVA.org:uu-380499DiVA, id: diva2:1306450
Available from: 2019-04-23 Created: 2019-04-23 Last updated: 2019-04-23Bibliographically approved

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Byberg, LiisaLind, LarsLjunggren, ÖstenMelhus, HåkanMichaëlsson, Karl

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Byberg, LiisaKilpelainen, Tuomas O.Lerch, Markus M.Lind, LarsLjunggren, ÖstenMedina-Gomez, CarolinaMelhus, HåkanMichaëlsson, KarlWilliams, Frances M. K.
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