No Causal Association between Insomnia and Gout: A Bidirectional Two-Sample Mendelian Randomization Study
DOI:
https://doi.org/10.54097/qzdf8q23Keywords:
Genetic Variants, Insomnia, Gout, Risk FactorsAbstract
Purpose: Previous observational studies have suggested an association between insomnia and gout. However, the causal nature of this relationship remains uncertain. This study aimed to investigate the bidirectional causal association between insomnia and gout using a Mendelian randomization (MR) analysis. Methods: A bidirectional two-sample MR analysis was conducted utilizing genome-wide association study (GWAS) summary data for insomnia and gout. Single-nucleotide polymorphisms (SNPs) significantly associated with insomnia and gout were used as instrumental variables. Causal effects were estimated using the inverse variance weighted (IVW) method, MR-Egger, and weighted median. Sensitivity analyses were then performed to assess potential pleiotropy and heterogeneity. Results: The MR analysis revealed no significant causal relationship between insomnia and the risk of gout (IVW OR=1.300, 95%CI:0.566-2.986, P=0.537). Similarly, reverse MR analysis showed no causal effect of gout on the risk of insomnia (IVW OR=1.005, 95%CI:0.999-1.011, P=0.099). The findings were consistent across all sensitivity analyses, with no evidence of horizontal pleiotropy or heterogeneity (P>0.05). Conclusion: This study found no evidence supporting a causal relationship between insomnia and gout in either direction. These findings suggest that previous associations observed in observational studies might be confounded by other factors. Further research using larger sample sizes and diverse populations is warranted to validate these results.
Downloads
References
[1] Marotto D, De Santis A, Chessa D, Firinu D, Del Giacco S. A Beacon in the Dark: Canakinumab. A New Therapeutic Perspective in Chronic Tophaceous Gout. Rheumatol Ther. 2018;5(1):303-310. doi:10.1007/s40744-018-0104-8. DOI: https://doi.org/10.1007/s40744-018-0104-8
[2] Chandratre P, Mallen C, Richardson J, et al. Health-related quality of life in gout in primary care: Baseline findings from a cohort study [published correction appears in Semin Arthritis Rheum. 2022 Feb;52:151800. doi: 10.1016/j.semarthrit. 2021. 02.009]. Semin Arthritis Rheum. 2018;48(1):61-69. doi:10. 1016/j. semarthrit.2017.12.005. DOI: https://doi.org/10.1016/j.semarthrit.2021.02.009
[3] Shi C, Zhou Z, Chi X, et al. Recent advances in gout drugs. Eur J Med Chem. 2023;245(Pt 1):114890. doi:10.1016/j. ejmech. 2022. 114890. DOI: https://doi.org/10.1016/j.ejmech.2022.114890
[4] Choi HK, McCormick N, Yokose C. Excess comorbidities in gout: the causal paradigm and pleiotropic approaches to care. Nat Rev Rheumatol. 2022;18(2):97-111. doi:10.1038/s41584-021-00725-9. DOI: https://doi.org/10.1038/s41584-021-00725-9
[5] Singh JA, Reddy SG, Kundukulam J. Risk factors for gout and prevention: a systematic review of the literature. Curr Opin Rheumatol. 2011;23(2):192-202. doi:10.1097/BOR. 0b013 e32 83438e13. DOI: https://doi.org/10.1097/BOR.0b013e3283438e13
[6] Riemann D, Dressle RJ, Benz F, et al. Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?. J Sleep Res. Published online May 29, 2024. doi:10.1111/jsr.14252. DOI: https://doi.org/10.1111/jsr.14252
[7] Taylor DJ, Mallory LJ, Lichstein KL, Durrence HH, Riedel BW, Bush AJ. Comorbidity of chronic insomnia with medical problems [published correction appears in Sleep. 2007 Jul 1;30 (7): table of contents]. Sleep. 2007;30(2):213-218. doi:10. 1093/ sleep/30.2.213. DOI: https://doi.org/10.1093/sleep/30.2.213
[8] Chami HA, Bechnak A, Isma'eel H, et al. Sleepless in Beirut: Sleep Difficulties in an Urban Environment With Chronic Psychosocial Stress. J Clin Sleep Med. 2019;15(4):603-614. Published 2019 Apr 15. doi:10.5664/jcsm.7724. DOI: https://doi.org/10.5664/jcsm.7724
[9] Wang Q, Chen B, Sheng D, et al. Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia. Microbiol Spectr. 2022;10(5):e0099822. doi: 10. 1128/spectrum.00998-22. DOI: https://doi.org/10.1128/spectrum.00998-22
[10] Wu Q, He P, Ye Z, et al. Sleep patterns, genetic susceptibility, and risk of new-onset gout: The UK Biobank prospective cohort study. J Psychosom Res. 2023;170:111381. doi: 10. 1016/ j. jpsychores.2023.111381. DOI: https://doi.org/10.1016/j.jpsychores.2023.111381
[11] Singh JA. Self-reported sleep quality and sleep disorders in people with physician-diagnosed gout: an Internet cross-sectional survey. Arthritis Res Ther. 2019;21(1):36. Published 2019 Jan 25. doi:10.1186/s13075-019-1821-2. DOI: https://doi.org/10.1186/s13075-019-1821-2
[12] Guevara-López U, Ayala-Guerrero F, Covarrubias-Gómez A, López-Muñoz FJ, Torres-González R. Effect of acute gouty arthritis on sleep patterns: a preclinical study. Eur J Pain. 2009;13(2):146-153. doi:10.1016/j.ejpain.2008.04.002. DOI: https://doi.org/10.1016/j.ejpain.2008.04.002
[13] Emdin CA, Khera AV, Kathiresan S. Mendelian Randomization. JAMA. 2017;318(19):1925-1926. doi: 10. 1001/ jama.2017.17219. DOI: https://doi.org/10.1001/jama.2017.17219
[14] Richmond RC, Davey Smith G. Mendelian Randomization: Concepts and Scope. Cold Spring Harb Perspect Med. 2022;12(1):a040501. Published 2022 Jan 4. doi:10.1101/ cshperspect. a040501. DOI: https://doi.org/10.1101/cshperspect.a040501
[15] Nguyen K, Mitchell BD. A Guide to Understanding Mendelian Randomization Studies. Arthritis Care Res (Hoboken). Published online July 19, 2024. doi:10.1002/acr.25400. DOI: https://doi.org/10.1002/acr.25400
[16] Sanderson E, Glymour MM, Holmes MV, et al. Mendelian randomization. Nat Rev Methods Primers. 2022;2:6. doi:10. 1038/ s43586-021-00092-5.
[17] Evans DM, Davey Smith G. Mendelian Randomization: New Applications in the Coming Age of Hypothesis-Free Causality. Annu Rev Genomics Hum Genet. 2015;16:327-350. doi:10.1146/annurev-genom-090314-050016. DOI: https://doi.org/10.1146/annurev-genom-090314-050016
[18] Lloyd K, Harrison S, Sallis HM, Davey Smith G, Munafò MR, Wootton RE. Exploring the Bidirectional Causal Pathways Between Smoking Behaviors and Headache: A Mendelian Randomization Study. Nicotine Tob Res. 2024;26(7):903-912. doi:10.1093/ntr/ntad173. DOI: https://doi.org/10.1093/ntr/ntad173
[19] Xu S, Gilliland FD, Conti DV. Elucidation of causal direction between asthma and obesity: a bi-directional Mendelian randomization study. Int J Epidemiol. 2019;48(3):899-907. doi:10.1093/ije/dyz070. DOI: https://doi.org/10.1093/ije/dyz070
[20] Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method [published correction appears in Eur J Epidemiol. 2017 May;32(5):391-392. doi: 10.1007/s10654-017-0276-5]. Eur J Epidemiol. 2017;32(5):377-389. doi:10.1007/s10654-017-0255-x. DOI: https://doi.org/10.1007/s10654-017-0255-x
[21] Ong JS, MacGregor S. Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner's perspective. Genet Epidemiol. 2019;43(6):609-616. doi:10.1002/gepi.22207. DOI: https://doi.org/10.1002/gepi.22207
[22] Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants. Epidemiology. 2017;28(1):30-42. doi:10.1097/EDE. 0000000000000559. DOI: https://doi.org/10.1097/EDE.0000000000000559
[23] Xue H, Liu S, Zeng L, Fan W. Causal effect of systemic lupus erythematosus on psychiatric disorders: A two-sample Mendelian randomization study. J Affect Disord. 2024; 347: 422-428. doi:10.1016/j.jad.2023.11.033. DOI: https://doi.org/10.1016/j.jad.2023.11.033
[24] Du W, He K, Liu X, Yin T, Xiao S, Zheng Y. Genetic association between asthma and alopecia areata: A two-sample Mendelian randomization study. Skin Res Technol. 2024;30(7): e13844. doi:10.1111/srt.13844. DOI: https://doi.org/10.1111/srt.13844
[25] Paulsamy P, Venkatesan K, Alshahrani S, et al. Alternate Warm and Cold Therapy (AWCT) on Uricemia, Sleep, Pain, Functional Ability, and Quality of Life (USPFQoL) in Patients with Gout: A Path Forward. J Healthc Eng. 2022;2022: 5471 575. Published 2022 Mar 9. doi:10.1155/2022/ 5471575. DOI: https://doi.org/10.1155/2022/5471575
[26] New-Tolley J, Reynolds AC, Appleton SL, et al. Sleep disorders and gout in Australian adults. BMC Rheumatol. 2021; 5(1):30. Published 2021 Aug 28. doi:10.1186/s41927-021-00199-y. DOI: https://doi.org/10.1186/s41927-021-00199-y
[27] Augusto Ferreira de Andrade C. Assessing qualitatively the impact of gout on sleep: any sleep was a dream far away until the gout flare resolved. Rheumatology (Oxford). 2018;57 (11): 1877-1878. doi:10.1093/rheumatology/key184. DOI: https://doi.org/10.1093/rheumatology/key184
[28] Sekula P, Del Greco M F, Pattaro C, Köttgen A. Mendelian Randomization as an Approach to Assess Causality Using Observational Data. J Am Soc Nephrol. 2016;27(11):3253-3265. doi:10.1681/ASN.2016010098. DOI: https://doi.org/10.1681/ASN.2016010098
Downloads
Published
Issue
Section
License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.