Machine Learning Analyses Reveal Circadian Features Predictive of Risk for Sleep Disturbance

Overview

Journal Nat Sci Sleep

Publisher Dove Medical Press

Date 2022 Oct 28

PMID 36304418

Authors

Rebeccah Overton

Aziz Zafar

Ziad Attia

Ahmet Ay

Krista K Ingram

Affiliations

Soon will be listed here.

Abstract

Introduction: Sleep disturbances often co-occur with mood disorders, with poor sleep quality affecting over a quarter of the global population. Recent advances in sleep and circadian biology suggest poor sleep quality is linked to disruptions in circadian rhythms, including significant associations between sleep features and circadian clock gene variants.

Methods: Here, we employ machine learning techniques, combined with statistical approaches, in a deeply phenotyped population to explore associations between clock genotypes, circadian phenotypes (diurnal preference and circadian phase), and risk for sleep disturbance symptoms.

Results: As found in previous studies, evening chronotypes report high levels of sleep disturbance symptoms. Using molecular chronotyping by measuring circadian phase, we extend these findings and show that individuals with a mismatch between circadian phase and diurnal preference report higher levels of sleep disturbance. We also report novel synergistic interactions in genotype combinations of and variants (PER3B (rs17031614)/ CRY1 (rs228716) and CLOCK3111 (rs1801260)/ CRY2 (rs10838524)) that yield strong associations with sleep disturbance, particularly in males.

Conclusion: Our results indicate that both direct and indirect mechanisms may impact sleep quality; sex-specific clock genotype combinations predictive of sleep disturbance may represent direct effects of clock gene function on downstream pathways involved in sleep physiology. In addition, the mediation of clock gene effects on sleep disturbance indicates circadian influences on the quality of sleep. Unraveling the complex molecular mechanisms at the intersection of circadian and sleep physiology is vital for understanding how genetic and behavioral factors influencing circadian phenotypes impact sleep quality. Such studies provide potential targets for further study and inform efforts to improve non-invasive therapeutics for sleep disorders.

Citing Articles

Machine learning analyses reveal circadian clock features predictive of anxiety among UK biobank participants.

Ventresca C, Mohamed W, Russel W, Ay A, Ingram K Sci Rep. 2023; 13(1):22304.

PMID: 38102312 PMC: 10724169. DOI: 10.1038/s41598-023-49644-7.

References

Archer S, Oster H . How sleep and wakefulness influence circadian rhythmicity: effects of insufficient and mistimed sleep on the animal and human transcriptome. J Sleep Res. 2015; 24(5):476-93. DOI: 10.1111/jsr.12307. View

Russo P, Biasi V, Cipolli C, Mallia L, Caponera E . Sleep habits, circadian preference, and school performance in early adolescents. Sleep Med. 2017; 29:20-22. DOI: 10.1016/j.sleep.2016.09.019. View

Liberman A, Halitjaha L, Ay A, Ingram K . Modeling Strengthens Molecular Link between Circadian Polymorphisms and Major Mood Disorders. J Biol Rhythms. 2018; 33(3):318-336. DOI: 10.1177/0748730418764540. View

Soria V, Martinez-Amoros E, Escaramis G, Valero J, Perez-Egea R, Garcia C . Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology. 2010; 35(6):1279-89. PMC: 3055337. DOI: 10.1038/npp.2009.230. View

Ebisawa T, Uchiyama M, Kajimura N, Mishima K, Kamei Y, Katoh M . Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome. EMBO Rep. 2001; 2(4):342-6. PMC: 1083867. DOI: 10.1093/embo-reports/kve070. View

Partonen T . Clock gene variants in mood and anxiety disorders. J Neural Transm (Vienna). 2012; 119(10):1133-45. DOI: 10.1007/s00702-012-0810-2. View

Vieira J, Jones A, Danon A, Sakuma M, Hoang N, Robles D . Human cryptochrome-1 confers light independent biological activity in transgenic Drosophila correlated with flavin radical stability. PLoS One. 2012; 7(3):e31867. PMC: 3299647. DOI: 10.1371/journal.pone.0031867. View

Lavebratt C, Sjoholm L, Soronen P, Paunio T, Vawter M, Bunney W . CRY2 is associated with depression. PLoS One. 2010; 5(2):e9407. PMC: 2827563. DOI: 10.1371/journal.pone.0009407. View

Nguyen C, Murray G, Anderson S, Filipowicz A, Ingram K . In vivo molecular chronotyping, circadian misalignment, and high rates of depression in young adults. J Affect Disord. 2019; 250:425-431. DOI: 10.1016/j.jad.2019.03.050. View

10.

Archer S, Robilliard D, Skene D, Smits M, Williams A, Arendt J . A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep. 2003; 26(4):413-5. DOI: 10.1093/sleep/26.4.413. View

11.

Patke A, Murphy P, Onat O, Krieger A, Ozcelik T, Campbell S . Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder. Cell. 2017; 169(2):203-215.e13. PMC: 5479574. DOI: 10.1016/j.cell.2017.03.027. View

12.

Albrecht U . Molecular Mechanisms in Mood Regulation Involving the Circadian Clock. Front Neurol. 2017; 8:30. PMC: 5293817. DOI: 10.3389/fneur.2017.00030. View

13.

Mistlberger R, Landry G, Marchant E . Sleep deprivation can attenuate light-induced phase shifts of circadian rhythms in hamsters. Neurosci Lett. 1998; 238(1-2):5-8. DOI: 10.1016/s0304-3940(97)00815-x. View

14.

Levandovski R, Dantas G, Fernandes L, Caumo W, Torres I, Roenneberg T . Depression scores associate with chronotype and social jetlag in a rural population. Chronobiol Int. 2011; 28(9):771-8. DOI: 10.3109/07420528.2011.602445. View

15.

Dardente H, Fortier E, Martineau V, Cermakian N . Cryptochromes impair phosphorylation of transcriptional activators in the clock: a general mechanism for circadian repression. Biochem J. 2006; 402(3):525-36. PMC: 1863574. DOI: 10.1042/BJ20060827. View

16.

Duffy J, Abbott S, Burgess H, Crowley S, Emens J, Epstein L . Workshop report. Circadian rhythm sleep-wake disorders: gaps and opportunities. Sleep. 2021; 44(5). PMC: 8120340. DOI: 10.1093/sleep/zsaa281. View

17.

Meyer P, Lafitte F, Bontempi G . minet: A R/Bioconductor package for inferring large transcriptional networks using mutual information. BMC Bioinformatics. 2008; 9:461. PMC: 2630331. DOI: 10.1186/1471-2105-9-461. View

18.

Utge S, Soronen P, Loukola A, Kronholm E, Ollila H, Pirkola S . Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. PLoS One. 2010; 5(2):e9259. PMC: 2823770. DOI: 10.1371/journal.pone.0009259. View

19.

Hida A, Kitamura S, Katayose Y, Kato M, Ono H, Kadotani H . Screening of clock gene polymorphisms demonstrates association of a PER3 polymorphism with morningness-eveningness preference and circadian rhythm sleep disorder. Sci Rep. 2014; 4:6309. PMC: 4158573. DOI: 10.1038/srep06309. View

20.

Fares S, Hermens D, Naismith S, White D, Hickie I, Robillard R . Clinical correlates of chronotypes in young persons with mental disorders. Chronobiol Int. 2015; 32(9):1183-91. DOI: 10.3109/07420528.2015.1078346. View