Fold change correlations reflect genotype-by-sex interactions in a population of inbred mouse strains. (A) Sex differences in body fat percentage vary substantially across 98 murine strains from the Hybrid Mouse Diversity Panel (fc = fold change). Fat percentage is elevated in approximately 50% of the strains, with apparent symmetry in the fold change directionality profile with respect to sex. (B) Distinct fold change correlation genes are observed for fat percentage, fat growth, and insulin resistance, therefore suggesting disparate genetic architectures. (C) Uty shows significant differential expression with respect to sex with elevation in males (negative fc) across strains (same strain organization as in A). (D) Due to the robust differential expression of Uty, and the variable sex-dependence of fat % across strains, the correspondence between sex and Uty expression is not associated with the correspondence between sex and fat percentage. (E) Xbp1 shows variable sex differences across strains without apparent differential expression (same strain organization as in A). (F) The strain-dependent Xbp1 fold changes are negatively associated with the fat percentage fold changes across strains. Therefore, the putative influence of sex on Xbp1 is associated with the putative influence of sex on fat percentage. (G) Overlapping the differentially expressed genes (|fc| >5%, FDR < 0.05) and fold change correlation genes (|midweight bicorrelation| > 0.2, FDR < 0.05) shows that fold change correlations identify distinct sets of genes for which sex differences in expression are consistent with sex differences in metabolic phenotypes.
