Integrating genome-wide association study and transcriptomic profiling identifies candidate genes underlying soluble solids content in melon ( <i>Cucumis melo</i> L.)

Abstract Soluble solids content (SSC) is a major determinant of flavor quality in melon fruit; however, the key genes regulating this trait remain poorly characterized. To elucidate the molecular basis of SSC variation, we performed genome-wide association studies (GWAS) using a diverse panel of 200 melon accessions, which detected 79 significant single nucleotide polymorphisms (SNPs) associated with SSC. Linkage disequilibrium (LD) decay analysis annotated 86 candidate genes within the associated genomic regions. To prioritize functionally relevant candidates, we further integrated transcriptome data from two genotypes with contrasting SSC levels, ‘San Ye Hua sugua’ (SYH; low SSC) and ‘Bai Sha Mi’ (BSM; high SSC). Comparative transcriptomic analysis revealed 18 candidate genes that were both GWAS-associated and differentially expressed between the two genotypes. Subsequent qRT-PCR validation confirmed concordant expression patterns for 14 of these candidates. Haplotype analysis demonstrated that natural variation at these loci was significantly correlated with SSC phenotypic variation across the population. Physicochemical component analysis revealed sucrose as the major driver of SSC accumulation. Five key candidate genes (MELO3C024714.2, MELO3C026992.2, MELO3C012177.2, MELO3C007562.2, and MELO3C007563.2) showed differential expression within the lipid metabolism-glyoxylate cycle-gluconeogenesis (LGG) pathway, implicating their synergistic involvement in energy metabolism and cellular homeostasis. In conclusion, our multi-omics approach identifies a robust set of candidate genes modulating melon SSC, providing mechanistic insight into fruit flavor formation and offering valuable genetic targets for marker-assisted or genomics-informed breeding of high-quality melons.