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Abstract Sarcopenia is a complex polygenic disease, and its molecular mechanism is still unclear. Whole lean body mass (WLBM) is a heritable trait predicting sarcopenia. To identify genomic loci underlying, we performed a whole‐exome sequencing (WES) of WLBM variation with high sequencing depth (more than 40*) in 101 Chinese subjects. We then replicated in the major findings in the large‐scale UK Biobank (UKB) cohort (N = 217,822) for WLBM. The results of four single‐nucleotide polymorphisms (SNPs) were significant both in the discovery stage and replication stage: SNP rs740681 (discovery p = 1.66 × 10–6, replication p = .05), rs2272303 (discovery p = 3.20 × 10–4, replication p = 3.10 × 10–4), rs11170413 (discovery p = 3.99 × 10–4, replication p = 2.90 × 10–4), and rs2272302 (discovery p = 9.13 × 10–4, replication p = 3.10 × 10–4). We combined p values of the significant SNPs. Functional annotations highlighted two candidate genes, including FZR1 and SOAT2, that may exert pleiotropic effects to the development of body mass. Our findings provide useful insights that further enhance our understanding of genetic interplay in sarcopenia.