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Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Zillikens, M Carola 
Demissie, Serkalem 
Hsu, Yi-Hsiang 
Yerges-Armstrong, Laura M 
Chou, Wen-Chi 

Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Description

Keywords

17-Hydroxysteroid Dehydrogenases, ADAMTS Proteins, Aldehyde Oxidoreductases, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Composition, Extracellular Matrix Proteins, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Regulatory Elements, Transcriptional, Thinness, Versicans

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

8

Publisher

Springer Science and Business Media LLC
Sponsorship
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
Medical Research Council (MC_UU_12015/1)
MRC (MC_PC_13048)
MRC (MC_PC_13046)
Medical Research Council (G1000143)
Cancer Research Uk (None)
Cancer Research Uk (None)
Cancer Research Uk (None)
Medical Research Council (G0401527)
Cancer Research Uk (None)
Department of Health (via National Institute for Health Research (NIHR)) (unknown)
National Institute for Health Research (NIHR) (NF-SI-0512-10114)
Medical Research Council (MR/N003284/1)
Medical Research Council (G0401527/1)
Medical Research Council (MC_PC_13048)
Medical Research Council (MC_PC_13046)