Sarcopenia exhibits causal association with benign prostatic hyperplasia (BPH, OR = 1.17, p = 0.043). Both conditions demonstrate local genetic linkage in a specific region of chromosome 3 (3:139954597–141,339,097, p = 2.16E-05), with 75 shared risk genes identified. Multi-omics mediational analysis identified 17 metabolites and proteins (e.g., EFNB2, ALDOC) mediating their association, ultimately revealing shared genetic architecture between sarcopenia and BPH. Here, EFNB2 is linked to sarcopenia.