Insomnia and the genetic overlap of sleep with depression and anxiety: a genomic structural equation modelling study
- 1Department of Physiology, School of Medicine, Brain and Cognition Research Center (BEYKOG), Istanbul Medipol University, Istanbul, Turkiye; Besikcizade Center f
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 ({Delta}AIC = 13.8; better in 98.6% of 500 Monte Carlo draws) and than shared content ({Delta}AIC = 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 ({Delta}AIC = -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.
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BibTeX
@misc{sakiroglu2026insomnia,
title = {{Insomnia and the genetic overlap of sleep with depression and anxiety: a genomic structural equation modelling study}},
author = {M. A. Sakiroglu and Y. Cicek and M. C. Celik and A. T. Altunc and D. Aslan and H. A. Velioglu},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.26366134},
url = {https://www.medrxiv.org/content/10.64898/2026.10.21.26366134v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Insomnia and the genetic overlap of sleep with depression and anxiety: a genomic structural equation modelling study
AU - M. A. Sakiroglu
AU - Y. Cicek
AU - M. C. Celik
AU - A. T. Altunc
AU - D. Aslan
AU - H. A. Velioglu
PY - 2026
DA - 2026/10/21
PB - medRxiv
DO - 10.64898/2026.10.21.26366134
UR - https://www.medrxiv.org/content/10.64898/2026.10.21.26366134v1
AB - 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 ({Delta}AIC = 13.8; better in 98.6% of 500 Monte Carlo draws) and than shared content ({Delta}AIC = 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 ({Delta}AIC = -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.
ER -