Metabolome-wide association studies for agronomic traits of rice

Identification of trait-associated metabolites will advance the knowledge and understanding of the biosynthetic and catabolic pathways that are relevant to the complex traits of interest. In the past, the association between metabolites (treated as quantitative traits) and genetic variants (e.g., SNPs) has been extensively studied using metabolomic quantitative trait locus (mQTL) mapping. Nevertheless, the research on the association between metabolites with agronomic traits has been inadequate. In practice, the regular approaches for QTL mapping analysis may be adopted for metabolites-phenotypes association analysis due to the similarity in data structure of these two types of researches. In the study, we compared four regular QTL mapping approaches, i.e., simple linear regression (LR), linear mixed model (LMM), Bayesian analysis with spike-slab priors (Bayes B) and least absolute shrinkage and selection operator (LASSO), by testing their performances on the analysis of metabolome-phenotype associations. Simulation studies showed that LASSO had the higher power and lower false positive rate than the other three methods. We investigated the associations of 839 metobolites with five agronomic traits in a collection of 533 rice varieties. The results implied that a total of 25 metabolites were significantly associated with five agronomic traits. Literature search and bioinformatics analysis indicated that the identified 25 metabolites are significantly involved in some growth and development processes potentially related to agronomic traits. We also explored the predictability of agronomic traits based on the 839 metabolites through cross-validation, which showed that metabolomic prediction was efficient and its application in plant breeding has been justified.