RT Journal
A1 Zhou, Shanshan
A1 Morgante, Fabio
A1 Geisz, Matthew S.
A1 Ma, Junwu
A1 Anholt, Robert R.H.
A1 Mackay, Trudy F.C.
T1 Systems genetics of the Drosophila metabolome
JF Genome Research 
JO Genome Research 
YR 2020 
FD March 01 
VO 30 
IS 3 
SP 392 
OP 405 
DO 10.1101/gr.243030.118 
UL http://genome.cshlp.org/content/30/3/392.abstract 
AB How effects of DNA sequence variants are transmitted through intermediate endophenotypes to modulate organismal traits remains a central question in quantitative genetics. This problem can be addressed through a systems approach in a population in which genetic polymorphisms, gene expression traits, metabolites, and complex phenotypes can be evaluated on the same genotypes. Here, we focused on the metabolome, which represents the most proximal link between genetic variation and organismal phenotype, and quantified metabolite levels in 40 lines of the Drosophila melanogaster Genetic Reference Panel. We identified sex-specific modules of genetically correlated metabolites and constructed networks that integrate DNA sequence variation and variation in gene expression with variation in metabolites and organismal traits, including starvation stress resistance and male aggression. Finally, we asked to what extent SNPs and metabolites can predict trait phenotypes and generated trait- and sex-specific prediction models that provide novel insights about the metabolomic underpinnings of complex phenotypes.