Genetic Variant in ACVR2B Is Associated with Lean Mass.

Abstract:

INTRODUCTION: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. METHODS: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. RESULTS: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. CONCLUSIONS: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.

journal_name

Med Sci Sports Exerc

authors

Klimentidis YC,Bea JW,Thompson P,Klimecki WT,Hu C,Wu G,Nicholas JS,Ryckman KK,Chen Z

doi

10.1249/MSS.0000000000000889

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

1270-5

issue

7

eissn

0195-9131

issn

1530-0315

journal_volume

48

pub_type

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