von Steimker, J.; Rey, E. L.; Stanschewski, C.; Wendenburg, R.; Klemmer, A.; Macho, M.; Thirumlaikumar, V.; Saber, N. O.; Skirycz, A.; Fernie, A. R.; Tester, M.; Alseekh, S.

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 4,688 metabolic features and identified over 1,000 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 signalling and metabolic pathways. Finally, we cloned and functional validated the roles of CYP76AD1 in betalamate accumulation, UGT91C1 in flavonoid glycosylation, and CYP72A154 and soyasapogenol B glucuronide galactosyltransferase (SGT) 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.