Lean body mass (LBM), a good index for skeletal muscle quantity and quality, is regarded as the important predictor of sarcopenia. To find the single nucleotide polymorphisms (SNP) loci and susceptibile genes associated with LBM, a genome-wide association study (GWAS) on the lean mass index (LMI) of 2 283 unrelated American Caucasian samples was performed and replicated on that of 1 000 unrelated American Caucasian samples. Then, a meta-analysis of the GWAS results and replication results was carried out. The genes UQCR, MBD3 and TCF3, located in the 19p13.3 region, are found to be associated with LMI. rs8697 (p=4.94×10^-3) and rs56122285 (p=2.59×10^-3) on UQCR gene are of eQTL (expression quantitative trait loci) effects, and rs8110543 (p=6.88×10^-3) and rs7252741 (p=1.22×10^-2) on MBD3 gene are also of eQTL effects, their DB scores are 1b and 1f respectively. The study further confirms the role of UQCR, MBD3 and TCF3 genes in lean body mass variability, and provides a new theoretical basis for the understanding of sarcopenia.