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Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study

posted on 21.04.2022, 18:53 by Junxi Liu, Rebecca C Richmond, Jack Bowden, Ciarrah Barry, Hassan S Dashti, Iyas Daghlas, Jacqueline M Lane, Samuel E Jones, Andrew R Wood, Timothy M Frayling, Alison K Wright, Matthew J Carr, Simon G Anderson, Richard Emsley, David Ray, Michael N Weedon, Richa Saxena, Deborah A Lawlor, Martin K Rutter
Objective: To examine the effects of sleep traits on glycated haemoglobin (HbA1c).

Research Design and Methods: This study triangulated evidence across multivariable regression (MVR), one-sample and two-sample Mendelian randomization (1SMR and 2SMR) including sensitivity analyses on the effects of 5 self-reported sleep traits (i.e., insomnia symptoms (difficulty initiating or maintaining sleep), sleep duration, daytime sleepiness, napping, chronotype) on HbA1c (in standard deviation (SD) units) in adults of European ancestry from the UK Biobank (for MVR and 1SMR analyses; n=336,999; mean (SD) age 57 (8) years, 54% female) and in the genome-wide association studies from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (for 2SMR analysis; n=46,368; 53 (11) years; 52% female).

Results: Across MV, 1SMR, 2SMR, and their sensitivity analyses we found a higher frequency of insomnia symptoms (usually vs sometimes or rarely/never) was associated with higher HbA1c (MVR: 0.05 SD units, 95% confidence interval (0.04 to 0.06), 1SMR: 0.52, (0.42 to 0.63), 2SMR: 0.24, (0.11 to 0.36)). Associations remained but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across, with some but not all, providing evidence of an effect.

Conclusions: Our results suggest that frequent insomnia symptoms causes higher HbA1c levels and by implication, that insomnia has a causal role in type 2 diabetes. These findings could have important implications for developing and evaluating strategies that improve sleep habits to reduce hyperglycaemia and prevent diabetes.


This work is supported by a Diabetes UK grant (17/0005700), which funds JL, AW and SJ’s salary. JL, RCR and DAL work in a unit that is funded by the University of Bristol and the UK Medical Research Council (MC_UU_00011/1 and MC_UU_00011/6) and DAL’s contribution to this paper was support by a grant from the British Heart Foundation (AA/18/7/34219). DAL is a NIHR Senior Investigator (NF-0616-10102) and BHF Chair in Cardiovascular Science and Clinical Epidemiology (CH/F/20/90003). RCR is a de Pass Vice Chancellor’s research fellow at the University of Bristol. HSD and RS are funded by the National Institute of Health ((R01DK107859). RS is funded by the National Institute of Health (R01DK105072). RS is awarded the Phyllis and Jerome Lyle Rappaport Massachusetts General Hospital Research Scholar Award. JB is funded by an Establishing Excellence in England (E3) grant awarded to the University of Exeter. DWR MRC programme grant MR/P023576/1. DWR is a Wellcome Investigator, Wellcome Trust (107849/Z/15/Z, 107849/A/15/Z). CB is supported by the Wellcome Trust via a PhD [218495/Z/19/Z].