Updated project metadata. Here, we have profiled 386 individuals in 80 cohorts of the BXD mouse genetic reference population across two environmental states through a metabolic phenotyping program including glucose response, exercise capacity, and cold response. To understand how the observed phenotypic differences are related to genetic variance, we generated a multilayered set of molecular phenotypes—genomics, transcriptomics, proteomics, and metabolomics across all cohorts, then modeled these molecular patterns with the phenotypic variance.