Cumulative Indicators of Circadian Rhythm Disturbance and its Clinical, Functional and Genetic Correlates in the Brisbane Longitudinal Twin Study
- 1Brain and Mind Centre, The University of Sydney
Abstract
BackgroundCircadian rhythm disturbances (CRDs) are transdiagnostic risk factors across mental disorders. We examined CRD-associated phenotypes, their heritability, and clinical, functional and genetic correlates, cross-sectionally, in young adults from the Brisbane Longitudinal Twin Study.
MethodsWe assessed 2,773 community-based participants (25.6{+/-}4.1 years; 57.8% female). Six CRD-associated phenotypes (seasonality, hypersomnia, social jetlag, delayed sleep, evening preference, sleep inertia) were included. Associations of CRD-load (number of CRDs) with clinical and functional outcomes, and with polygenic risk scores (PRS) for mental health, physical health, and sleep/circadian traits, were tested using linear, negative binomial, or logistic regression, with family-clustered standard errors. Heritability of CRD-phenotypes was estimated using structural equation modelling.
ResultsAlmost half the sample (49.2%) reported experiencing [≥]1 CRD-phenotype and 20.5% reported [≥]2. Four CRD-phenotypes (hypersomnia, social jetlag, delayed sleep, evening preference) were significantly heritable (h2=0.19-0.48). Higher CRD-load was associated with greater psychological distress ({beta}=0.96, p<0.001), more psychological symptoms (incidence rate ratio [IRR]=1.07-1.40), higher odds of a full-threshold mental disorder (OR=1.28, p<0.001), and greater functional impairment (days-in-bed, IRR=1.55; days-out-of-role, IRR=1.43). In genotyped participants (n=2,301), CRD-load was associated with mood-disorder PRS (major depression [OR=1.14, p=0.003] and bipolar disorder [OR=1.14, p=0.002]) but not PRSs for schizophrenia, attention deficit hyperactivity disorder, autism, neuroticism or anxiety. Trends towards increased PRSs for metabolic traits did not survive Bonferroni-correction.
ConclusionsCRD-load was associated with clinical symptoms, functional impairment, and mood-related genetic liability. These findings support further evaluation of brief assessments of circadian-associated phenotypes for identifying young people at greater clinical burden and informing circadian-focused prevention and early intervention strategies.
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BibTeX
@misc{shin2026cumulative,
title = {{Cumulative Indicators of Circadian Rhythm Disturbance and its Clinical, Functional and Genetic Correlates in the Brisbane Longitudinal Twin Study}},
author = {M. Shin and E. Tonini and J. S. Carpenter and B. L. Mitchell and B. Couvy-Duchesne and S. H. Park and R. Parker and E. M. Byrne and S. Hockey and A. Treneman and T. To and N. Bhattacharya and A. Shim and E. M. Scott and N. A. Gillespie and N. G. Martin and J. Scott and S. Medland and J. Crouse and I. B. Hickie},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.26362400},
url = {https://www.medrxiv.org/content/10.64898/2026.09.13.26362400v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cumulative Indicators of Circadian Rhythm Disturbance and its Clinical, Functional and Genetic Correlates in the Brisbane Longitudinal Twin Study
AU - M. Shin
AU - E. Tonini
AU - J. S. Carpenter
AU - B. L. Mitchell
AU - B. Couvy-Duchesne
AU - S. H. Park
AU - R. Parker
AU - E. M. Byrne
AU - S. Hockey
AU - A. Treneman
AU - T. To
AU - N. Bhattacharya
AU - A. Shim
AU - E. M. Scott
AU - N. A. Gillespie
AU - N. G. Martin
AU - J. Scott
AU - S. Medland
AU - J. Crouse
AU - I. B. Hickie
PY - 2026
DA - 2026/09/13
PB - medRxiv
DO - 10.64898/2026.09.13.26362400
UR - https://www.medrxiv.org/content/10.64898/2026.09.13.26362400v1
AB - BackgroundCircadian rhythm disturbances (CRDs) are transdiagnostic risk factors across mental disorders. We examined CRD-associated phenotypes, their heritability, and clinical, functional and genetic correlates, cross-sectionally, in young adults from the Brisbane Longitudinal Twin Study. MethodsWe assessed 2,773 community-based participants (25.6{+/-}4.1 years; 57.8% female). Six CRD-associated phenotypes (seasonality, hypersomnia, social jetlag, delayed sleep, evening preference, sleep inertia) were included. Associations of CRD-load (number of CRDs) with clinical and functional outcomes, and with polygenic risk scores (PRS) for mental health, physical health, and sleep/circadian traits, were tested using linear, negative binomial, or logistic regression, with family-clustered standard errors. Heritability of CRD-phenotypes was estimated using structural equation modelling. ResultsAlmost half the sample (49.2%) reported experiencing [≥]1 CRD-phenotype and 20.5% reported [≥]2. Four CRD-phenotypes (hypersomnia, social jetlag, delayed sleep, evening preference) were significantly heritable (h2=0.19-0.48). Higher CRD-load was associated with greater psychological distress ({beta}=0.96, p<0.001), more psychological symptoms (incidence rate ratio [IRR]=1.07-1.40), higher odds of a full-threshold mental disorder (OR=1.28, p<0.001), and greater functional impairment (days-in-bed, IRR=1.55; days-out-of-role, IRR=1.43). In genotyped participants (n=2,301), CRD-load was associated with mood-disorder PRS (major depression [OR=1.14, p=0.003] and bipolar disorder [OR=1.14, p=0.002]) but not PRSs for schizophrenia, attention deficit hyperactivity disorder, autism, neuroticism or anxiety. Trends towards increased PRSs for metabolic traits did not survive Bonferroni-correction. ConclusionsCRD-load was associated with clinical symptoms, functional impairment, and mood-related genetic liability. These findings support further evaluation of brief assessments of circadian-associated phenotypes for identifying young people at greater clinical burden and informing circadian-focused prevention and early intervention strategies.
ER -