@article{e87e0ac91017413098c442843f480735,
title = "Assessing the Causal Role of Sleep Traits on Glycated Hemoglobin: A Mendelian Randomization Study",
abstract = "OBJECTIVE: To examine the effects of sleep traits on glycated hemoglobin (HbA1c). RESEARCH DESIGN AND METHODS: This study triangulated evidence across multivariable regression (MVR) and one- (1SMR) and two-sample Mendelian randomization (2SMR) including sensitivity analyses on the effects of five self-reported sleep traits (i.e., insomnia symptoms [difficulty initiating or maintaining sleep], sleep duration, daytime sleepiness, napping, and chronotype) on HbA1c (in 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 MVR, 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% CI 0.04-0.06]; 1SMR 0.52 [0.42-0.63]; 2SMR 0.24 [0.11-0.36]). Associations remained, but point estimates were somewhat attenuated after excluding participants with diabetes. For other sleep traits, there was less consistency across methods, with some but not all providing evidence of an effect. CONCLUSIONS: Our results suggest that frequent insomnia symptoms cause 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 hyperglycemia and prevent diabetes.",
author = "Junxi Liu and Richmond, {Rebecca C.} and Jack Bowden and Ciarrah Barry and Dashti, {Hassan S.} and Iyas Daghlas and Lane, {Jacqueline M.} and Jones, {Samuel E.} and Wood, {Andrew R.} and Frayling, {Timothy M.} and Wright, {Alison K.} and Carr, {Matthew J.} and Anderson, {Simon G.} and Emsley, {Richard A.} and Ray, {David W.} and Weedon, {Michael N.} and Richa Saxena and Lawlor, {Deborah A.} and Rutter, {Martin K.}",
note = "Funding Information: This work is supported by a Diabetes UK grant (17/0005700), which funds salaries of J.L., A.K.W., and S.E.J. J.L., R.C.R., and D.A.L. work in a unit that is funded by the University of Bristol and the U.K. Medical Research Council (MRC) (MC_UU_00011/1 and MC_UU_00011/6), and contribution of D.A.L. to this paper was support by a grant from the British Heart Foundation (AA/18/7/ 34219). D.A.L. is an NIHR Senior Investigator (NF-0616-10102) and British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology (CH/F/20/90003). R.C.R. is a de Pass Vice Chancellor{\textquoteright}s research fellow at the University of Bristol. H.S.D. and R.S. are funded by National Institutes of Health (NIH) grants R01DK107859, and R.S. is funded by NIH grant R01DK105072. R.S. is a recipient of the Phyllis and Jerome Lyle Rappaport Massachusetts General Hospital Research Scholar Award. J.B. is funded by an Establishing Excellence in England (E3) grant awarded to the University of Exeter. D.W.R. is funded by MRC programme grant MR/P023576/1 and is a Wellcome Investigator, Wellcome Trust (107849/Z/15/Z and 107849/A/15/Z). C.B. is supported by the Wellcome Trust via a PhD (218495/Z/19/Z). Funding Information: Acknowledgments. The authors thank the participants and researchers from the UKB who contributed or collected data. The authors also thank Dr. Eleanor Sanderson (Medical Research Council Integrative Epidemiology Unit, University of Bristol) for providing statistical support on multivariable MR. Data on glycemic traits were contributed by MAGIC investigators and downloaded from www.magicinvestigators.org. This research was conducted using the UKB Resource under application 6818. Funding. This work is supported by a Diabetes UK grant (17/0005700), which funds salaries of J.L., A.K.W., and S.E.J. J.L., R.C.R., and D.A.L. work in a unit that is funded by the University of Bristol and the U.K. Medical Research Council (MRC) (MC_UU_00011/1 and MC_UU_00011/6), and contribution of D.A.L. to this paper was support by a grant from the British Heart Foundation (AA/18/7/ 34219). D.A.L. is an NIHR Senior Investigator (NF-0616-10102) and British Heart Foundation Chair in Cardiovascular Science and Clinical Epidemiology (CH/F/20/90003). R.C.R. is a de Pass Vice Chancellor{\textquoteright}s research fellow at the University of Bristol. H.S.D. and R.S. are funded by National Institutes of Health (NIH) grants R01DK107859, and R.S. is funded by NIH grant R01DK105072. R.S. is a recipient of the Phyllis and Jerome Lyle Rappaport Massachusetts General Hospital Research Scholar Award. J.B. is funded by an Establishing Excellence in England (E3) grant awarded to the University of Exeter. D.W.R. is funded by MRC programme grant MR/P023576/1 and is a Wellcome Investigator, Wellcome Trust (107849/Z/15/Z and 107849/A/15/Z). C.B. is supported by the Wellcome Trust via a PhD (218495/Z/19/Z). Duality of Interest. M.K.R. reports receiving research funding from Novo Nordisk and consultancy fees from Novo Nordisk and Roche Diabetes Care and has a modest shareholding in GlaxoSmithKline, all unrelated to this work. J.B. reports receiving consultancy fees from Novartis, unrelated to this work. D.A.L. has received support from Roche Diagnostics and Medtronic Ltd for research unrelated to this work. No other potential conflicts of interest relevant to this article were reported. Author Contributions. J.L. affirms that this manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. J.L. and R.C.R. carried out the data analysis. M.K.R. conceived the idea for the study. M.K.R., R.A.E., D.W.R., S.G.A., M.J.C., M.N.W., T.M.F., A.R.W., J.B., and D.A.L. obtained funds for the project. R.C.R., J.B., D.A.L., and M.K.R. designed the study, including developing the analysis plan. J.B. and C.B. developed the novel one-sample pleiotropy robust analyses. J.L. and R.C.R. carried out the data analysis. J.L., R.C.R., J.B., D.A.L., and M.K.R. wrote the initial draft, with subsequent input from other authors. All authors made critical revisions to the paper. J.L., R.C.R., and D.A.L. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2022 by the American Diabetes Association.",
year = "2022",
month = apr,
day = "1",
doi = "10.2337/dc21-0089",
language = "English",
volume = "45",
pages = "772--781",
journal = "Diabetes Care",
issn = "0149-5992",
publisher = "American Diabetes Association",
number = "4",
}
