Genetic–Geographic–Chemical Framework of Polyporus umbellatus Reveals Lineage-Specific Chemotypes for Elite Medicinal Line Breeding

<i>Polyporus umbellatus</i> is a valuable fungus with both dietary and medicinal applications. However, heterogeneous germplasm and chemical variability constrain its sustainable use. To elucidate the drivers of this variation, whole-genome resequencing and metabolic profiling were integrated. Genome-wide analysis of representative accessions revealed six distinct genetic clusters across China, identifying the Qinling-Daba Mountains as a putative center of diversity. Population analysis indicated severe genetic erosion with significant heterozygote deficits, likely driven by inbreeding and long-term clonal propagation. Multivariate analysis demonstrated that genetic lineage, rather than traditional commercial morphotypes (Zhushiling and Jishiling), is the primary determinant of metabolite accumulation. Specific lineages were identified as superior germplasm candidates: Group 2 consistently exhibited the highest genetic potential for accumulating steroids, whereas Group 4 attained the highest polysaccharide yield. Although the global genetic-chemical correlation was weak, implying environmental plasticity, the distinct clustering of superior lineages confirms that core accumulation patterns are genetically canalized. These findings advocate for shifting quality control from morphological grading to molecular-assisted selection. Ultimately, this framework provides an evidence-based foundation for urgent in situ conservation to restore genetic diversity and facilitates precision breeding of high-efficacy cultivars.