Disentangling the genetics of lean mass
Copyright policy )Disentangling the genetics of lean mass
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.
- Cellzome, GSK, Middlesex, UK.
- Indiana University United States
- University of Washington United States
- Uppsala University Sweden
- Boston College United States
Adipose Tissue/metabolism, Male, Skeletal muscle, Body Fluid Compartments/metabolism, Body composition, Medical and Health Sciences, 796, Engineering, Versicans, ADAMTS Proteins, Absorptiometry, Photon, 80 and over, Electric Impedance, 2.1 Biological and endogenous factors, Aetiology, European Continental Ancestry Group/genetics, Aged, 80 and over, Extracellular Matrix Proteins, ADAMTS Proteins/genetics, RNA-Binding Proteins, Skeletal, Single Nucleotide, Body Fluid Compartments, Middle Aged, Wessex Classification Subject Headings::Oncology. Pathology.::Genetics, metabolic profile, Photon, body fat, Phenotype, Adipose Tissue, Body fat, Type 4/genetics, Melanocortin, Body Composition, Muscle, Female, Type 4, Receptor, Adult, meta-analysis of genome-wide association studies, Versicans/genetics, Adolescent, 610, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Metabolic profile, Skeletal/metabolism, meta-Analysis of genome-wide association studies, Extracellular Matrix Proteins/genetics, Polymorphism, Single Nucleotide, White People, Young Adult, Meta-analysis of genome-wide association studies, Genetics, Humans, Receptor, Melanocortin, Type 4/genetics, skeletal muscle, Absorptiometry, Polymorphism, Muscle, Skeletal, Aged, body composition, Body Composition/genetics, Muscle, Skeletal/metabolism, Nutrition & Dietetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics, Prevention, Human Genome, RNA-Binding Proteins/genetics, EMC MM-01-39-02, EMC MM-01-39-09-A, Genome-Wide Association Study
Adipose Tissue/metabolism, Male, Skeletal muscle, Body Fluid Compartments/metabolism, Body composition, Medical and Health Sciences, 796, Engineering, Versicans, ADAMTS Proteins, Absorptiometry, Photon, 80 and over, Electric Impedance, 2.1 Biological and endogenous factors, Aetiology, European Continental Ancestry Group/genetics, Aged, 80 and over, Extracellular Matrix Proteins, ADAMTS Proteins/genetics, RNA-Binding Proteins, Skeletal, Single Nucleotide, Body Fluid Compartments, Middle Aged, Wessex Classification Subject Headings::Oncology. Pathology.::Genetics, metabolic profile, Photon, body fat, Phenotype, Adipose Tissue, Body fat, Type 4/genetics, Melanocortin, Body Composition, Muscle, Female, Type 4, Receptor, Adult, meta-analysis of genome-wide association studies, Versicans/genetics, Adolescent, 610, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Metabolic profile, Skeletal/metabolism, meta-Analysis of genome-wide association studies, Extracellular Matrix Proteins/genetics, Polymorphism, Single Nucleotide, White People, Young Adult, Meta-analysis of genome-wide association studies, Genetics, Humans, Receptor, Melanocortin, Type 4/genetics, skeletal muscle, Absorptiometry, Polymorphism, Muscle, Skeletal, Aged, body composition, Body Composition/genetics, Muscle, Skeletal/metabolism, Nutrition & Dietetics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics, Prevention, Human Genome, RNA-Binding Proteins/genetics, EMC MM-01-39-02, EMC MM-01-39-09-A, Genome-Wide Association Study
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