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 1,493 single-nucleotide polymorphisms (SNPs) 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 2,760 non-Hispanic and Hispanic White postmenopausal women from the Women’s Health Initiative (WHI) Observational Study. We assessed replication of our top findings in a meta-analysis of twenty genome-wide association studies (n=38,292) conducted by the CHARGE Consortium Musculoskeletal Working Group. RESULTS: We identified 32 SNPs that had 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 x 10). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, mysostatin, 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 to women. Additional large-scale studies will be needed to confirm our findings in different populations.
ASJC Scopus subject areas
- Orthopedics and Sports Medicine
- Physical Therapy, Sports Therapy and Rehabilitation