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BMC Medicine
Published in: BMC Medicine 1/2021

01-12-2021 | Insomnia | Research article

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

Authors: Maxime M. Bos, Neil J. Goulding, Matthew A. Lee, Amy Hofman, Mariska Bot, René Pool, Lisanne S. Vijfhuizen, Xiang Zhang, Chihua Li, Rima Mustafa, Matt J. Neville, Ruifang Li-Gao, Stella Trompet, Marian Beekman, Nienke R. Biermasz, Dorret I. Boomsma, Irene de Boer, Constantinos Christodoulides, Abbas Dehghan, Ko Willems van Dijk, Ian Ford, Mohsen Ghanbari, Bastiaan T. Heijmans, M. Arfan Ikram, J. Wouter Jukema, Dennis O. Mook-Kanamori, Fredrik Karpe, Annemarie I. Luik, L. H. Lumey, Arn M. J. M. van den Maagdenberg, Simon P. Mooijaart, Renée de Mutsert, Brenda W. J. H. Penninx, Patrick C. N. Rensen, Rebecca C. Richmond, Frits R. Rosendaal, Naveed Sattar, Robert A. Schoevers, P. Eline Slagboom, Gisela M. Terwindt, Carisha S. Thesing, Kaitlin H. Wade, Carolien A. Wijsman, Gonneke Willemsen, Aeilko H. Zwinderman, Diana van Heemst, Raymond Noordam, Deborah A. Lawlor

Published in: BMC Medicine | Issue 1/2021

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Abstract

Background

Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.

Methods

We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.

Results

We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (− 0.08 standard deviation (SD)[95% confidence interval (CI) − 0.12, − 0.03] in AMV and − 0.03SD [− 0.07, − 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (− 0.04SD [− 0.08, 0.00] in AMV and − 0.05SD [− 0.09, − 0.02] in MR), and lower phospholipids in very large HDL particles (− 0.04SD [− 0.08, 0.002] in AMV and − 0.05SD [− 0.08, − 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.

Conclusions

Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
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Literature
1.
Wu Y, Zhai L, Zhang D. Sleep duration and obesity among adults: a meta-analysis of prospective studies. Sleep Med. 2014;15(12):1456–62.PubMedCrossRef
2.
Xi B, He D, Zhang M, Xue J, Zhou D. Short sleep duration predicts risk of metabolic syndrome: a systematic review and meta-analysis. Sleep Med Rev. 2014;18(4):293–7.PubMedCrossRef
3.
Itani O, Jike M, Watanabe N, Kaneita Y. Short sleep duration and health outcomes: a systematic review, meta-analysis, and meta-regression. Sleep Med. 2017;32:246–56.PubMedCrossRef
4.
Jike M, Itani O, Watanabe N, Buysse DJ, Kaneita Y. Long sleep duration and health outcomes: a systematic review, meta-analysis and meta-regression. Sleep Med Rev. 2018;39:25–36.PubMedCrossRef
5.
Cappuccio FP, Cooper D, D'Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J. 2011;32(12):1484–92.PubMedCrossRef
6.
Ge L, Guyatt G, Tian J, Pan B, Chang Y, Chen Y, Li H, Zhang J, Li Y, Ling J, et al. Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: systematic review and meta-analysis of prospective cohort studies. Sleep Med Rev. 2019;48:101215.PubMedCrossRef
7.
Sofi F, Cesari F, Casini A, Macchi C, Abbate R, Gensini GF. Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol. 2014;21(1):57–64.PubMedCrossRef
8.
Zheng B, Yu C, Lv J, Guo Y, Bian Z, Zhou M, Yang L, Chen Y, Li X, Zou J, et al. Insomnia symptoms and risk of cardiovascular diseases among 0.5 million adults: a 10-year cohort. Neurology. 2019;93(23):e2110–20.PubMedPubMedCentralCrossRef
9.
Knutson KL, von Schantz M. Associations between chronotype, morbidity and mortality in the UK biobank cohort. Chronobiol Int. 2018;35(8):1045–53.PubMedPubMedCentral
10.
Petrov ME, Kim Y, Lauderdale D, Lewis CE, Reis JP, Carnethon MR, Knutson K, Glasser SJ. Longitudinal associations between objective sleep and lipids: the CARDIA study. Sleep. 2013;36(11):1587–95.PubMedPubMedCentralCrossRef
11.
Bos MM, Noordam R, van den Berg R, de Mutsert R, Rosendaal FR, Blauw GJ, Rensen PCN, Biermasz NR, van Heemst D. Associations of sleep duration and quality with serum and hepatic lipids: the Netherlands Epidemiology of Obesity Study. J Sleep Res. 2019;28(4):e12776.PubMedCrossRef
12.
13.
Noordam R, Bos MM, Wang H, Winkler TW, Bentley AR, Kilpelainen TO, de Vries PS, Sung YJ, Schwander K, Cade BE, et al. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration. Nat Commun. 2019;10(1):5121.PubMedPubMedCentralCrossRef
14.
15.
Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27(8):1133–63.PubMedCrossRef
16.
Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, Laurin C, Burgess S, Bowden J, Langdon R, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408
17.
Lane JM, Jones SE, Dashti HS, Wood AR, Aragam KG, van Hees VT, Strand LB, Winsvold BS, Wang H, Bowden J, et al. Biological and clinical insights from genetics of insomnia symptoms. Nat Genet. 2019;51(3):387–93.PubMedPubMedCentralCrossRef
18.
Daghlas I, Dashti HS, Lane J, Aragam KG, Rutter MK, Saxena R, Vetter C. Sleep duration and myocardial infarction. J Am Coll Cardiol. 2019;74(10):1304–14.PubMedPubMedCentralCrossRef
19.
Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, de Leeuw CA, Benjamins JS, Munoz-Manchado AB, Nagel M, et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nat Genet. 2019;51(3):394–403.PubMedCrossRef
20.
Dashti HS, Jones SE, Wood AR, Lane JM, van Hees VT, Wang H, Rhodes JA, Song Y, Patel K, Anderson SG, et al. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates. Nat Commun. 2019;10(1):1100.PubMedPubMedCentralCrossRef
21.
Jones SE, Lane JM, Wood AR, van Hees VT, Tyrrell J, Beaumont RN, Jeffries AR, Dashti HS, Hillsdon M, Ruth KS, et al. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms. Nat Commun. 2019;10(1):343.PubMedPubMedCentralCrossRef
22.
Lawlor DA, Tilling K, Davey Smith G. Triangulation in aetiological epidemiology. Int J Epidemiol. 2016;45(6):1866–86.PubMed
23.
Wijsman CA, Westendorp RG, Verhagen EA, Catt M, Slagboom PE, de Craen AJ, Broekhuizen K, van Mechelen W, van Heemst D, van der Ouderaa F, et al. Effects of a web-based intervention on physical activity and metabolism in older adults: randomized controlled trial. J Med Internet Res. 2013;15(11):e233.PubMedPubMedCentralCrossRef
24.
Lumey LH, Stein AD, Kahn HS, van der Pal-de Bruin KM, Blauw GJ, Zybert PA, Susser ES. Cohort profile: the Dutch Hunger Winter families study. Int J Epidemiol. 2007;36(6):1196–204.PubMedCrossRef
25.
Snijder MB, Galenkamp H, Prins M, Derks EM, Peters RJG, Zwinderman AH, Stronks K. Cohort profile: the Healthy Life in an Urban Setting (HELIUS) study in Amsterdam, The Netherlands. BMJ Open. 2017;7(12):e017873.PubMedPubMedCentralCrossRef
26.
van Oosterhout WP, Weller CM, Stam AH, Bakels F, Stijnen T, Ferrari MD, Terwindt GM. Validation of the web-based LUMINA questionnaire for recruiting large cohorts of migraineurs. Cephalalgia. 2011;31(13):1359–67.PubMedCrossRef
27.
Penninx BW, Beekman AT, Smit JH, Zitman FG, Nolen WA, Spinhoven P, Cuijpers P, De Jong PJ, Van Marwijk HW, Assendelft WJ, et al. The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. Int J Methods Psychiatr Res. 2008;17(3):121–40.PubMedPubMedCentralCrossRef
28.
Willemsen G, de Geus EJ, Bartels M, van Beijsterveldt CE, Brooks AI, Estourgie-van Burk GF, Fugman DA, Hoekstra C, Hottenga JJ, Kluft K, et al. The Netherlands twin register biobank: a resource for genetic epidemiological studies. Twin Res Hum Genet. 2010;13(3):231–45.PubMedCrossRef
29.
de Mutsert R, den Heijer M, Rabelink TJ, Smit JW, Romijn JA, Jukema JW, de Roos A, Cobbaert CM, Kloppenburg M, le Cessie S, et al. The Netherlands Epidemiology of Obesity (NEO) study: study design and data collection. Eur J Epidemiol. 2013;28(6):513–23.PubMedCrossRef
30.
Ikram MA, Brusselle GGO, Murad SD, van Duijn CM, Franco OH, Goedegebure A, Klaver CCW, Nijsten TEC, Peeters RP, Stricker BH, et al. The Rotterdam Study: 2018 update on objectives, design and main results. Eur J Epidemiol. 2017;32(9):807–50.PubMedPubMedCentralCrossRef
31.
Anujuo K, Stronks K, Snijder MB, Jean-Louis G, Ogedegbe G, Agyemang C. Ethnic differences in self-reported sleep duration in the Netherlands--the HELIUS study. Sleep Med. 2014;15(9):1115–21.PubMedCrossRef
32.
Stronks K, Snijder MB, Peters RJ, Prins M, Schene AH, Zwinderman AH. Unravelling the impact of ethnicity on health in Europe: the HELIUS study. BMC Public Health. 2013;13:402.PubMedPubMedCentralCrossRef
33.
van Beijsterveldt CE, Groen-Blokhuis M, Hottenga JJ, Franic S, Hudziak JJ, Lamb D, Huppertz C, de Zeeuw E, Nivard M, Schutte N, et al. The Young Netherlands twin register (YNTR): longitudinal twin and family studies in over 70,000 children. Twin Res Hum Genet. 2013;16(1):252–67.PubMedCrossRef
34.
de Weerd A, de Haas S, Otte A, Trenite DK, van Erp G, Cohen A, de Kam M, van Gerven J. Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life. Epilepsia. 2004;45(11):1397–404.PubMedCrossRef
35.
Kettunen J, Demirkan A, Wurtz P, Draisma HH, Haller T, Rawal R, Vaarhorst A, Kangas AJ, Lyytikainen LP, Pirinen M, et al. Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA. Nat Commun. 2016;7:11122.PubMedPubMedCentralCrossRef
36.
Karpe F, Vasan SK, Humphreys SM, Miller J, Cheeseman J, Dennis AL, Neville MJ. Cohort profile: the Oxford biobank. Int J Epidemiol. 2018;47(1):21–21g.PubMedCrossRef
37.
Shepherd J, Blauw GJ, Murphy MB, Cobbe SM, Bollen EL, Buckley BM, Ford I, Jukema JW, Hyland M, Gaw A, et al. The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk. Am J Cardiol. 1999;84(10):1192–7.PubMedCrossRef
38.
Blauw LL, Li-Gao R, Noordam R, de Mutsert R, Trompet S, Berbee JFP, Wang Y, van Klinken JB, Christen T, van Heemst D, et al. CETP (cholesteryl ester transfer protein) concentration: a genome-wide association study followed by Mendelian randomization on coronary artery disease. Circ Genom Precis Med. 2018;11(5):e002034.PubMedCrossRef
39.
Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360(9346):1623–30.PubMedCrossRef
40.
Soininen P, Kangas AJ, Würtz P, Suna T, Ala-Korpela M. Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circ Cardiovasc Genet. 2015;8(1):192–206.PubMedCrossRef
41.
Sliz E, Kettunen J, Holmes MV, Williams CO, Boachie C, Wang Q, Mannikko M, Sebert S, Walters R, Lin K, et al. Metabolomic consequences of genetic inhibition of PCSK9 compared with statin treatment. Circulation. 2018;138(22):2499–512.PubMedPubMedCentralCrossRef
42.
Wurtz P, Havulinna AS, Soininen P, Tynkkynen T, Prieto-Merino D, Tillin T, Ghorbani A, Artati A, Wang Q, Tiainen M, et al. Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts. Circulation. 2015;131(9):774–85.PubMedPubMedCentralCrossRef
43.
Team RDC: R: a language and environment for statistical computing. 2008.
44.
Noordam R, Young WJ, Salman R, Kanters JK, van den Berg ME, van Heemst D, Lin HJ, Barreto SM, Biggs ML, Biino G, et al. Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals. J Am Coll Cardiol. 2019;73(24):3118–31.PubMedCrossRef
45.
Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan N, Thompson J. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017;36(11):1783–802.PubMedPubMedCentralCrossRef
46.
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.PubMedPubMedCentralCrossRef
47.
Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40(4):304–14.PubMedPubMedCentralCrossRef
48.
Gu Z, Gu L, Eils R, Schlesner M, Brors B. circlize implements and enhances circular visualization in R. Bioinformatics. 2014;30(19):2811–2.PubMedCrossRef
49.
Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32(18):2847–9.CrossRefPubMed
50.
Santos Ferreira DL, Williams DM, Kangas AJ, Soininen P, Ala-Korpela M, Smith GD, Jarvelin MR, Lawlor DA. Association of pre-pregnancy body mass index with offspring metabolic profile: analyses of 3 European prospective birth cohorts. PLoS Med. 2017;14(8):e1002376.PubMedPubMedCentralCrossRef
51.
Davies SK, Ang JE, Revell VL, Holmes B, Mann A, Robertson FP, Cui N, Middleton B, Ackermann K, Kayser M, et al. Effect of sleep deprivation on the human metabolome. Proc Natl Acad Sci U S A. 2014;111(29):10761–6.PubMedPubMedCentralCrossRef
52.
Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, Collins R, Danesh J. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132–40.CrossRef
53.
C. Reactive Protein Coronary Heart Disease Genetics Collaboration, Wensley F, Gao P, Burgess S, Kaptoge S, Di Angelantonio E, Shah T, Engert JC, Clarke R, Davey-Smith G, et al. Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data. BMJ. 2011;342:d548.CrossRef
54.
Fuertes-Martin R, Correig X, Vallve JC, Amigo N. Title: Human serum/plasma glycoprotein analysis by (1) H-NMR, an emerging method of inflammatory assessment. J Clin Med. 2020;9(2):354.
55.
Connelly MA, Otvos JD, Shalaurova I, Playford MP, Mehta NN. GlycA, a novel biomarker of systemic inflammation and cardiovascular disease risk. J Transl Med. 2017;15(1):219.PubMedPubMedCentralCrossRef
56.
Costello LC, Franklin RB. Plasma citrate homeostasis: how it is regulated; and its physiological and clinical implications. an important, but neglected, relationship in medicine. HSOA J Hum Endocrinol. 2016;1(1):005.
57.
Kandeger A, Egilmez U, Sayin AA, Selvi Y. The relationship between night eating symptoms and disordered eating attitudes via insomnia and chronotype differences. Psychiatry Res. 2018;268:354–7.PubMedCrossRef
58.
Pinkosky SL, Newton RS, Day EA, Ford RJ, Lhotak S, Austin RC, Birch CM, Smith BK, Filippov S, Groot PHE, et al. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat Commun. 2016;7:13457.PubMedPubMedCentralCrossRef
59.
Ference BA, Ray KK, Catapano AL, Ference TB, Burgess S, Neff DR, Oliver-Williams C, Wood AM, Butterworth AS, Di Angelantonio E, et al. Mendelian randomization study of ACLY and cardiovascular disease. N Engl J Med. 2019;380(11):1033–42.PubMedCrossRef
60.
Ballantyne CM, McKenney JM, MacDougall DE, Margulies JR, Robinson PL, Hanselman JC, Lalwani ND. Effect of ETC-1002 on serum low-density lipoprotein cholesterol in hypercholesterolemic patients receiving statin therapy. Am J Cardiol. 2016;117(12):1928–33.PubMedCrossRef
61.
Ballantyne CM, Banach M, Mancini GBJ, Lepor NE, Hanselman JC, Zhao X, Leiter LA. Efficacy and safety of bempedoic acid added to ezetimibe in statin-intolerant patients with hypercholesterolemia: a randomized, placebo-controlled study. Atherosclerosis. 2018;277:195–203.PubMedCrossRef
62.
Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, Hindy G, Holm H, Ding EL, Johnson T, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380(9841):572–80.PubMedPubMedCentralCrossRef
63.
Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, Chaitman BR, Holme IM, Kallend D, Leiter LA, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089–99.PubMedCrossRef
64.
Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22.PubMedCrossRef
65.
Ding M, Rexrode KM. A review of lipidomics of cardiovascular disease highlights the importance of isolating lipoproteins. Metabolites. 2020;10(4):163.
66.
Liu HM, Hu Q, Zhang Q, Su GY, Xiao HM, Li BY, Shen WD, Qiu X, Lv WQ, Deng HW. Causal effects of genetically predicted cardiovascular risk factors on chronic kidney disease: a two-sample Mendelian randomization study. Front Genet. 2019;10:415.PubMedPubMedCentralCrossRef
67.
Di Angelantonio E, Danesh J, Eiriksdottir G, Gudnason V. Renal function and risk of coronary heart disease in general populations: new prospective study and systematic review. PLoS Med. 2007;4(9):e270.PubMedPubMedCentralCrossRef
68.
Lotta LA, Scott RA, Sharp SJ, Burgess S, Luan J, Tillin T, Schmidt AF, Imamura F, Stewart ID, Perry JR, et al. Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: a Mendelian randomisation analysis. PLoS Med. 2016;13(11):e1002179.PubMedPubMedCentralCrossRef
69.
70.
Jackson CL, Patel SR, Jackson WB 2nd, Lutsey PL, Redline S. Agreement between self-reported and objectively measured sleep duration among white, black, Hispanic, and Chinese adults in the United States: Multi-Ethnic Study of Atherosclerosis. Sleep. 2018;41(6):zsy057.
Metadata
Title
Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses
Authors
Maxime M. Bos
Neil J. Goulding
Matthew A. Lee
Amy Hofman
Mariska Bot
René Pool
Lisanne S. Vijfhuizen
Xiang Zhang
Chihua Li
Rima Mustafa
Matt J. Neville
Ruifang Li-Gao
Stella Trompet
Marian Beekman
Nienke R. Biermasz
Dorret I. Boomsma
Irene de Boer
Constantinos Christodoulides
Abbas Dehghan
Ko Willems van Dijk
Ian Ford
Mohsen Ghanbari
Bastiaan T. Heijmans
M. Arfan Ikram
J. Wouter Jukema
Dennis O. Mook-Kanamori
Fredrik Karpe
Annemarie I. Luik
L. H. Lumey
Arn M. J. M. van den Maagdenberg
Simon P. Mooijaart
Renée de Mutsert
Brenda W. J. H. Penninx
Patrick C. N. Rensen
Rebecca C. Richmond
Frits R. Rosendaal
Naveed Sattar
Robert A. Schoevers
P. Eline Slagboom
Gisela M. Terwindt
Carisha S. Thesing
Kaitlin H. Wade
Carolien A. Wijsman
Gonneke Willemsen
Aeilko H. Zwinderman
Diana van Heemst
Raymond Noordam
Deborah A. Lawlor
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Insomnia
Published in
BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-021-01939-0

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