Insomnia and the genetic overlap of sleep with depression and anxiety: a genomic structural equation modelling study
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Insomnia, depression and anxiety co-occur and share genetic liability, but a genetic correlation cannot show whether that liability is spread across the sleep domain or concentrated in insomnia, a diagnostic criterion for depression and generalized anxiety disorder. We applied genomic structural equation modelling to ten genome-wide association studies and fitted a four-factor model of sleep, internalizing (depression and anxiety), psychotic-bipolar and metabolic liability. A model linking the sleep and internalizing domains only through their factor correlation was inadmissible, and we compared, under one decision rule, each one-parameter link that could repair it: domain-wide links, an insomnia-specific cross-loading, and residual covariances representing shared diagnostic content, of which three were admissible. The insomnia cross-loading fitted better than the only admissible domain-wide alternative (ΔAIC = 13.8; better in 98.6% of 500 Monte Carlo draws) and than shared content (ΔAIC = 96.9), and placing it on psychotic-bipolar or metabolic liability was inadmissible. Under this model the insomnia pathway carried 56.3% of the sleep-internalizing covariance (95% CI 45.6-67.0%). A second sleep pathway improved fit (ΔAIC = -33.3), but with three sleep indicators its location was not identifiable, and across the equivalent models the insomnia share ranged from 0% to 127.0%. At the variant level, no internalizing lead departed from depression-anxiety proportionality after correction, and internalizing leads replicated in FinnGen, with partial sample overlap, whereas sleep leads did not (60.4%; P = 0.17). How concentrated the overlap is will require finer sleep phenotypes to establish. Among single-link models, insomnia is the best-supported location of the overlap.
Source: medRxiv
Language: English
Topic: Sleep and related disorders
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
Funders: University of Bristol, National Institutes of Health, Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund
OpenAlex ID: W7223319370