Through selective signal elimination analysis, we identified 13 candidate genes that might be associated with lambing trait: BMPR2, ID2, SMAD7, PLCZ, PAK1, ELOC, RAD50, H2A, H2B, THBS1, RBX1, H4, and ABCC4. Functional enrichment analysis of these genes showed that the TGF-β signaling pathway, renal cell carcinoma, non-homologous terminal junction, NETs pathway, ABC transporter, and other pathways may be involved in the regulation of lambing trait in Hotan sheep, thus influencing the fertility of this population. Here, RAD50 is linked to hereditary clear cell renal cell carcinoma.