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The genetics of circadian rhythms, sleep and health.

ABSTRACT: Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and psychiatric illness including depression (1,2). Mouse models of clock mutants recapitulate these deficits, implicating mechanistic and causal links between SCRD and disease pathophysiology (3-5). Importantly, treating clock disruption reverses and attenuates these adverse health states in animal models (6,7), thus establishing the circadian system as a novel therapeutic target. Significantly, circadian and clock-controlled gene mutations have recently been identified by Genome-Wide Association Studies (GWAS) in the aetiology of sleep, mental health and metabolic disorders. This review will focus upon the genetics of circadian rhythms in sleep and health.

SUBMITTER: Jagannath A

PROVIDER: S-EPMC5886477 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The genetics of circadian rhythms, sleep and health.

Jagannath Aarti A Taylor Lewis L Wakaf Zeinab Z Vasudevan Sridhar R SR Foster Russell G RG

Human molecular genetics 20171001 R2

Circadian rhythms are 24-h rhythms in physiology and behaviour generated by molecular clocks, which serve to coordinate internal time with the external world. The circadian system is a master regulator of nearly all physiology and its disruption has major consequences on health. Sleep and circadian rhythm disruption (SCRD) is a ubiquitous feature in today's 24/7 society, and studies on shift-workers have shown that SCRD can lead not only to cognitive impairment, but also metabolic syndrome and p ...[more]

PMID: 28977444

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Project description:ImportanceObservational studies have associated anorexia nervosa with circadian rhythms and sleep traits. However, the direction of causality and the extent of confounding by psychosocial comorbidities in these associations are unknown.ObjectivesTo investigate the association between anorexia nervosa and circadian and sleep traits through mendelian randomization and to test the associations between a polygenic risk score (PRS) for anorexia nervosa and sleep disorders in a clinical biobank.Design, setting, and participantsThis genetic association study used bidirectional 2-sample mendelian randomization with summary-level genetic associations between anorexia nervosa (from the Psychiatric Genomics Consortium) and chronotype and sleep traits (primarily from the UK Biobank). The inverse-variance weighted method, in addition to other sensitivity approaches, was used. From the clinical Mass General Brigham (MGB) Biobank (n = 47 082), a PRS for anorexia nervosa was calculated for each patient and associations were tested with prevalent sleep disorders derived from electronic health records. Patients were of European ancestry. All analyses were performed between February and August 2023.ExposuresGenetic instruments for anorexia nervosa, chronotype, daytime napping, daytime sleepiness, insomnia, and sleep duration.Main outcomes and measuresChronotype, sleep traits, risk of anorexia nervosa, and sleep disorders derived from a clinical biobank.ResultsThe anorexia nervosa genome-wide association study included 16 992 cases (87.7%-97.4% female) and 55 525 controls (49.6%-63.4% female). Genetic liability for anorexia nervosa was associated with a more morning chronotype (β = 0.039; 95% CI, 0.006-0.072), and conversely, genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (β = 0.178; 95% CI, 0.042-0.315). Associations were robust in sensitivity and secondary analyses. Genetic liability for insomnia was associated with increased risk of anorexia nervosa (β = 0.369; 95% CI, 0.073-0.666); however, sensitivity analyses indicated bias due to horizontal pleiotropy. The MGB Biobank analysis included 47 082 participants with a mean (SD) age of 60.4 (17.0) years and 25 318 (53.8%) were female. A PRS for anorexia nervosa was associated with organic or persistent insomnia in the MGB Biobank (odds ratio, 1.10; 95% CI, 1.03-1.17). No associations were evident for anorexia nervosa with other sleep traits.Conclusions and relevanceThe results of this study suggest that in contrast to other metabo-psychiatric diseases, anorexia nervosa is a morningness eating disorder and further corroborate findings implicating insomnia in anorexia nervosa. Future studies in diverse populations and with subtypes of anorexia nervosa are warranted.

Dataset Information

The genetics of circadian rhythms, sleep and health.

Publications

The genetics of circadian rhythms, sleep and health.

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