Genome-wide association study of circadian rhythmicity in 71,500 UK Biobank participants and polygenic association with mood instability

Ferguson, A. et al. (2018) Genome-wide association study of circadian rhythmicity in 71,500 UK Biobank participants and polygenic association with mood instability. EBioMedicine, 35, pp. 279-287. (doi:10.1016/j.ebiom.2018.08.004) (PMID:30120083) (PMCID:PMC6154782)

Ferguson, A. et al. (2018) Genome-wide association study of circadian rhythmicity in 71,500 UK Biobank participants and polygenic association with mood instability. EBioMedicine, 35, pp. 279-287. (doi:10.1016/j.ebiom.2018.08.004) (PMID:30120083) (PMCID:PMC6154782)

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Abstract

Background: Circadian rhythms are fundamental to health and are particularly important for mental wellbeing. Disrupted rhythms of rest and activity are recognised as risk factors for major depressive disorder and bipolar disorder. Methods: We conducted a genome-wide association study (GWAS) of low relative amplitude (RA), an objective measure of rest-activity cycles derived from the accelerometer data of 71,500 UK Biobank participants. Polygenic risk scores (PRS) for low RA were used to investigate potential associations with psychiatric phenotypes. Outcomes: Two independent genetic loci were associated with low RA, within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25 Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a locus within Meis Homeobox 1 (MEIS1). There were no significant genetic correlations between low RA and any of the psychiatric phenotypes assessed. However, PRS for low RA was significantly associated with mood instability across multiple PRS thresholds (at PRS threshold 0·05: OR = 1·02, 95% CI = 1·01–1·02, p = 9·6 × 10−5), and with major depressive disorder (at PRS threshold 0·1: OR = 1·03, 95% CI = 1·01–1·05, p = 0·025) and neuroticism (at PRS threshold 0·5: Beta = 0·02, 95% CI = 0·007–0·04, p = 0·021). Interpretation: Overall, our findings contribute new knowledge on the complex genetic architecture of circadian rhythmicity and suggest a putative biological link between disrupted circadian function and mood disorder phenotypes, particularly mood instability, but also major depressive disorder and neuroticism. Funding: Medical Research Council (MR/K501335/1).

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Biello, Professor Stephany and Lyall, Dr Laura and Bailey, Dr Mark and Niedzwiedz, Dr Claire and Cavanagh, Professor Jonathan and Ward, Mr Joey and Wyse, Dr Cathy and Johnston, Ms Keira and Cullen, Dr Breda and Pell, Professor Jill and Ferguson, Amy and Mackay, Dr Daniel and Lyall, Dr Donald and Strawbridge, Dr Rona and Graham, Dr Nicholas
Authors: Ferguson, A., Lyall, L. M., Ward, J., Strawbridge, R. J., Cullen, B., Graham, N., Niedzwiedz, C. L., Johnston, K. J.A., Mackay, D., Biello, S. M., Pell, J. P., Cavanagh, J., McIntosh, A. M., Doherty, A., Bailey, M. E.S., Lyall, D. M., Wyse, C. A., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:EBioMedicine
Publisher:Elsevier
ISSN:2352-3964
ISSN (Online):2352-3964
Published Online:14 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in EBioMedicine 35: 279-287
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
632341MRC Doctoral Training Grant 2013/14, 2014/15 and 2015/16George BaillieMedical Research Council (MRC)MR/K501335/1MVLS GRADUATE SCHOOL
3021310Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health
3021820A machine learning approach to understanding comorbidity between mental and physical health conditionsJill PellMedical Research Council (MRC)MR/R024774/1HW - Public Health