The Interplay Between Sleep and Mental Health: A Genetic Perspective.

Although many facets of sleep, including subjective, behavioral, and neurophysiological features, are closely linked with psychiatric disorders, the natures of these relationships are generally unclear. A given alteration in sleep could reflect a cause (that may mediate genetic risk), consequence, symptom, trigger, epiphenomenon due to shared determinants, or some combination of these. In principle, genetic approaches can be informative: 1) by identifying specific genetic influences on disease mediated by or shared with sleep, which could help the search for biological mechanisms and therapeutic targets, and 2) by providing evidence for causality, which could suggest interventions for modifiable sleep traits. Here, we summarize recent human quantitative and molecular genetic studies on sleep and psychiatric disease, including twin and genome-wide association studies. Despite evidence for shared heritability across many domains, notably depression and insomnia, the field is in its early stages and faces significant challenges including the following: 1) putative causal effects are small, phenotypically nonspecific, not resolved to specific gene pathways, and often bidirectional; 2) most current discovery cohorts are demographically biased and do not capture profound age-related changes in sleep and its genetic architecture; 3) group-level analyses ignore patient-to-patient heterogeneity, including the presence or absence of specific sleep alterations; and 4) a paucity of objective, brain-based data in genetically informative samples hampers making connections with sleep neurophysiology. Nonetheless, as ever-growing genetic tools and resources still hold great potential for translational bridges between basic model systems, human epidemiology, and personalized clinical care, genetic approaches will still likely be needed to reveal sleep's roles in maintaining mental health.