Disentangling the genetics of lean mass.
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
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
White People
/ genetics
Young Adult
Journal
The American journal of clinical nutrition
ISSN: 1938-3207
Titre abrégé: Am J Clin Nutr
Pays: United States
ID NLM: 0376027
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
22
03
2018
accepted:
11
09
2018
pubmed:
6
2
2019
medline:
23
10
2019
entrez:
6
2
2019
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 30721968
pii: S0002-9165(22)03110-0
doi: 10.1093/ajcn/nqy272
pmc: PMC6500901
doi:
Substances chimiques
ADAMTSL3 protein, human
0
Extracellular Matrix Proteins
0
MC4R protein, human
0
RNA-Binding Proteins
0
Receptor, Melanocortin, Type 4
0
TNRC6B protein, human
0
VCAN protein, human
0
Versicans
126968-45-4
Alpha-Ketoglutarate-Dependent Dioxygenase FTO
EC 1.14.11.33
FTO protein, human
EC 1.14.11.33
ADAMTS Proteins
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
276-287Subventions
Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG024827
Pays : United States
Organisme : NCCDPHP CDC HHS
ID : U01 DP006266
Pays : United States
Organisme : Medical Research Council
ID : MR/N003284/1
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR002369
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110113
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR041398
Pays : United States
Organisme : Cancer Research UK
ID : 14136
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0401527
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG051129
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Organisme : NIAMS NIH HHS
ID : U01 AR066160
Pays : United States
Organisme : Medical Research Council
ID : G1000143
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107786
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12015/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
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