| Sleep dysfunction and stress susceptibility are co-morbid complex traits, which often precede and predispose patients to a variety of neuropsychiatric diseases. Here, I demonstrate a dynamic genetic landscape associated with 328 stress and sleep traits in a chronically stressed (C57BL/6JxA/J) F2 mouse population and identify specific transcriptional networks in the striatum as points of convergence between these different phenotypes. These findings were complemented by an analogous study in (C57BL/6Jx129) F2 mice, which identified convergent networks and shared genetics of gene expression in the hippocampus, hypothalamus, cortex, and thalamus. I further integrated these F2 mouse studies with genetic and transcriptional data from human neuropsychiatric cohorts and causal mouse studies, revealing pathways through which disease pathogenesis can impinge upon specific regional gene networks and affect sleep and stress traits. This work highlights molecular evidence for the interplay between sleep, stress, and neuropsychiatric disease and provides a comprehensive framework to interrogate the shared mechanisms underlying these comorbid traits. |
