title: Genetic Variant in ACVR2B Is Associated with Lean Mass.
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.
authors: 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.
authors: Yann C
authors: YC
authors: Klimentidis
authors: Jennifer W
authors: JW
authors: Bea
authors: Patricia
authors: P
authors: Thompson
authors: Walter T
authors: WT
authors: Klimecki
authors: Chengcheng
authors: C
authors: Hu
authors: Guanglin
authors: G
authors: Wu
authors: J Skye
authors: JS
authors: Nicholas
authors: Kelli K
authors: KK
authors: Ryckman
authors: Zhao
authors: Z
authors: Chen
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics*; D000368:Aged; D000483:Alleles; D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000502:physiology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C579679:ACVR2B protein, human; D030301:Activin Receptors, Type II