Multi‐tissue Metabolic GWAS and Drought‐Responsive Multi‐omics Reveal the Genetic Basis of the Quinoa Metabolome

ABSTRACT Quinoa ( Chenopodium quinoa ) is a nutrient‐rich pseudocereal with diverse specialized metabolites, yet the genetic basis of this metabolic diversity is poorly understood. Here we integrate whole‐genome sequencing and multi‐tissue metabolic profiling of 603 quinoa accessions. We detected 4688 metabolic features and identified over 1000 metabolites in seeds, leaves, and roots. Using multi‐tissue genome‐wide association, we mapped the genetic architecture of quinoa metabolome by identifying 584 quantitative trait loci (QTL) and prioritized 219 candidate genes across 58 major QTL governing saponin, betalain, and flavonoid biosynthesis. Moreover, we constructed a drought‐responsive multi‐omics regulatory network and uncovered additional key genes involved in quinoa stress signaling and metabolic pathways. Finally, we cloned and functional validated the roles of cytochrome P450 76AD1 (CYP76AD1) in betalamate accumulation, UDP‐glycosyltransferase (UGT91C1) in flavonoid glycosylation, and CYP72A154 and soyasapogenol B glucuronide galactosyltransferase in saponin biosynthesis. This multi‐omic framework provides a high‐resolution map of the quinoa metabolome and a foundation for breeding nutrient‐rich and stress‐resilient quinoa cultivars.