Genetic Variant in ACVR2B Is Associated with Lean Mass

Yann C Klimentidis; Jennifer W Bea; Patricia Thompson; Walter T Klimecki; Chengcheng Hu; Guanglin Wu; J Skye Nicholas; Kelli K Ryckman; Zhao Chen

doi:10.1249/MSS.0000000000000889

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Genetic Variant in ACVR2B Is Associated with Lean Mass

Journal article

Peer reviewed

Genetic Variant in ACVR2B Is Associated with Lean Mass

Yann C Klimentidis, Jennifer W Bea, Patricia Thompson, Walter T Klimecki, Chengcheng Hu, Guanglin Wu, J Skye Nicholas, Kelli K Ryckman and Zhao Chen

Medicine and science in sports and exercise, Vol.48(7), pp.1270-1275

07/2016

DOI: 10.1249/MSS.0000000000000889

PMCID: PMC4911281

PMID: 26848890

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https://www.ncbi.nlm.nih.gov/pmc/articles/4911281View

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Abstract

Low lean mass (LM) is a risk factor for chronic disease, a major cause of disability and diminished quality of life, and is a heritable trait. However, relatively few specific genetic factors have been identified as potentially influencing this trait. In this study, we selected 1493 single-nucleotide polymorphisms (SNP) in 155 candidate genes involved in anabolic, catabolic, growth hormone, and other related pathways and examined their association with LM, assessed by dual-energy x-ray absorptiometry, in a sample of 2760 non-Hispanic and Hispanic white postmenopausal women from the Women's Health Initiative (WHI) Observational Study. We assessed the replication of our top findings in a meta-analysis of 20 genome-wide association studies (n = 38,292) conducted by the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Musculoskeletal Working Group. We identified 32 SNPs that had nominally significant associations with LM in the WHI cohort. In the replication stage, we find that SNP rs2276541 in the activin A receptor, type IIB (ACVR2B), was significantly associated with LM (β = 0.15, P = 2.17 × 10). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, myostatin, and has previously been identified in a candidate gene study as a determinant of skeletal muscle mass. Our findings support a previously proposed role of ACVR2B allelic variation as a determinant of muscle mass and extend prior findings in men and women. Additional large-scale studies will be needed to confirm our findings in different populations.

Body Mass Index

Humans

Middle Aged

Risk Factors

Genotype

Muscle, Skeletal - physiology

Phenotype

Body Composition - genetics

Activin Receptors, Type II - genetics

Alleles

Female

Aged

Polymorphism, Single Nucleotide

Details

Title: Subtitle: Genetic Variant in ACVR2B Is Associated with Lean Mass
Creators: Yann C Klimentidis - 1Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ; 2University of Arizona Cancer Center, University of Arizona, Tucson, AZ; 3Department of Nutritional Sciences, University of Arizona, Tucson, AZ; 4Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ; 5Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ; 6Department of Epidemiology and Pediatrics, University of Iowa, Iowa City, IA
Jennifer W Bea
Patricia Thompson
Walter T Klimecki
Chengcheng Hu
Guanglin Wu
J Skye Nicholas
Kelli K Ryckman
Zhao Chen
Resource Type: Journal article
Publication Details: Medicine and science in sports and exercise, Vol.48(7), pp.1270-1275
DOI: 10.1249/MSS.0000000000000889
PMID: 26848890
PMCID: PMC4911281
NLM abbreviation: Med Sci Sports Exerc
ISSN: 0195-9131
eISSN: 1530-0315
Publisher: United States
Grant note: N01 WH042126 / WHI NIH HHS N01 WH032105 / WHI NIH HHS N01WH32111 / WHI NIH HHS N01 WH032118 / WHI NIH HHS N01 WH042122 / WHI NIH HHS N01 WH032119 / WHI NIH HHS N01WH32106 / WHI NIH HHS N01 WH042112 / WHI NIH HHS N01 WH042131 / WHI NIH HHS N01 WH42124 / NIH HHS N01WH24152 / WHI NIH HHS N01 WH042116 / WHI NIH HHS N01WH32101 / WHI NIH HHS N01WH42108 / WHI NIH HHS N01 WH042132 / WHI NIH HHS N01 WH042107 / WHI NIH HHS N01 WH042123 / WHI NIH HHS N01WH42113 / WHI NIH HHS N01 WH032102 / WHI NIH HHS N01WH44221 / WHI NIH HHS N01WH32109 / WHI NIH HHS P30 ES006694 / NIEHS NIH HHS N01 WH042117 / WHI NIH HHS N01 WH042119 / WHI NIH HHS R01 AG027373 / NIA NIH HHS N01WH32108 / WHI NIH HHS N01 WH042110 / WHI NIH HHS N01 WH042120 / WHI NIH HHS N01WH32113 / WHI NIH HHS N01 WH042114 / WHI NIH HHS N01 WH042129 / WHI NIH HHS N01WH32100 / WHI NIH HHS N01 WH042118 / WHI NIH HHS N01 WH042125 / WHI NIH HHS N01WH32112 / WHI NIH HHS N01 WH042121 / WHI NIH HHS N01WH22110 / WHI NIH HHS N01 WH042111 / WHI NIH HHS K01 DK095032 / NIDDK NIH HHS N01 WH32115 / WHI NIH HHS N01 WH042115 / WHI NIH HHS N01 WH042130 / WHI NIH HHS N01 WH032122 / WHI NIH HHS N01WH42109 / WHI NIH HHS
Language: English
Date published: 07/2016
Academic Unit: Stead Family Department of Pediatrics; Epidemiology
Record Identifier: 9983996065202771

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