The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study

Junxi Liu; Rebecca C Richmond; Emma L Anderson; Jack Bowden; Ciarrah-Jane S Barry; Hassan S Dashti; Iyas S Daghlas; Jacqueline M Lane; Simon D Kyle; Céline Vetter; Claire L Morrison; Samuel E Jones; Andrew R Wood; Timothy M Frayling; Alison K Wright; Matthew J Carr; Simon G Anderson; Richard A Emsley; David W Ray; Michael N Weedon; Richa Saxena; Martin K Rutter; Deborah A Lawlor

doi:10.1038/s41598-024-58007-9

The role of accelerometer-derived sleep traits on glycated haemoglobin and glucose levels: a Mendelian randomization study

Sci Rep. 2024 Jun 28;14(1):14962. doi: 10.1038/s41598-024-58007-9.

Authors

Junxi Liu^#^{1

2

3}, Rebecca C Richmond^#^{4

5}, Emma L Anderson^{4

5

6}, Jack Bowden^{4

7}, Ciarrah-Jane S Barry^{4

5}, Hassan S Dashti^{8

9

10}, Iyas S Daghlas^{8

9

10}, Jacqueline M Lane^{8

9

10}, Simon D Kyle¹¹, Céline Vetter¹², Claire L Morrison¹³, Samuel E Jones¹⁴, Andrew R Wood¹⁵, Timothy M Frayling¹⁵, Alison K Wright¹⁶, Matthew J Carr^{16

17

18}, Simon G Anderson^{19

20}, Richard A Emsley²¹, David W Ray^{22

23}, Michael N Weedon¹⁵, Richa Saxena^{8

9

10

24}, Martin K Rutter^{17

25

26}, Deborah A Lawlor^{4

5

27}

Affiliations

¹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. ieu_james.liu@bristol.ac.uk.
² Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. ieu_james.liu@bristol.ac.uk.
³ Nuffield Department of Population Health, Oxford Population Health, University of Oxford, Oxford, UK. ieu_james.liu@bristol.ac.uk.
⁴ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁶ Division of Psychiatry, University College of London, London, UK.
⁷ College of Medicine and Health, The University of Exeter, Exeter, UK.
⁸ Centre for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Sir Jules Thorn Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
¹² Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
¹³ Department of Psychology & Neuroscience and Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
¹⁴ Institute for Molecular Medicine Finland, University of Helsinki, Uusimaa, Finland.
¹⁵ Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK.
¹⁶ Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
¹⁷ NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
¹⁸ National Institute for Health Research (NIHR) Greater Manchester Patient Safety Translational Research Centre, University of Manchester, Manchester, UK.
¹⁹ George Alleyne Chronic Disease Research Centre, Caribbean Institute of Health Research, University of the West Indies, Kingston, Jamaica.
²⁰ Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
²¹ Department of Biostatistics and Health Informatics, King's College London, London, UK.
²² Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK.
²³ NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
²⁴ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
²⁵ Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK.
²⁶ Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
²⁷ National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and The University of Bristol, Bristol, UK.

^# Contributed equally.

Abstract

Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.

Keywords: Diabetes; Epidemiology; Glucose; Glycated haemoglobin; Mendelian randomization; Sleepiness.

MeSH terms

Accelerometry*
Adult
Aged
Blood Glucose* / analysis
Female
Glycated Hemoglobin* / analysis
Glycated Hemoglobin* / metabolism
Humans
Male
Mendelian Randomization Analysis*
Middle Aged
Self Report
Sleep Initiation and Maintenance Disorders / genetics
Sleep* / genetics
Sleep* / physiology

Substances

Glycated Hemoglobin
Blood Glucose
hemoglobin A1c protein, human