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Short or Long Sleep Duration and CKD: A Mendelian Randomization Study
Open accessAbstract
Significance Statement Poor sleep is known to be related to kidney function impairment. Using the UK Biobank cohort, including individuals self-reporting regular sleep patterns of short, intermediate, or long duration, the authors found that short or long sleep duration was associated with higher prevalence of CKD. In the genetic analysis, the genetic risk score for short but not long sleep duration was significantly related to a higher risk of CKD stages 3–5, suggesting causal effects of short sleep duration on CKD. Two-sample Mendelian randomization analysis, using the independent meta-analysis results of kidney function from the CKDGen Consortium genome-wide association study, also showed significant causal estimates of short sleep duration on CKD. Clinicians may thus consider encouraging patients to avoid short-duration sleeping behavior to reduce the risk of CKD. Background Studies have found sleeping behaviors, such as sleep duration, to be associated with kidney function and cardiovascular disease risk. However, whether short or long sleep duration is a causative factor for kidney function impairment has been rarely studied. Methods We studied data from participants aged 40–69 years in the UK Biobank prospective cohort, including 25,605 self-reporting short-duration sleep (<6 hours per 24 hours), 404,550 reporting intermediate-duration sleep (6–8 hours), and 35,659 reporting long-duration sleep (≥9 hours) in the clinical analysis. Using logistic regression analysis, we investigated the observational association between the sleep duration group and prevalent CKD stages 3–5, analyzed by logistic regression analysis. We performed Mendelian randomization (MR) analysis involving 321,260 White British individuals using genetic instruments (genetic variants linked with short- or long-duration sleep behavior as instrumental variables). We performed genetic risk score analysis as a one-sample MR and extended the finding with a two-sample MR analysis with CKD outcome information from the independent CKDGen Consortium genome-wide association study meta-analysis. Results Short or long sleep duration clinically associated with higher prevalence of CKD compared with intermediate duration. The genetic risk score for short (but not long) sleep was significantly related to CKD (per unit reflecting a two-fold increase in the odds of the phenotype; adjusted odds ratio, 1.80; 95% confidence interval, 1.25 to 2.60). Two-sample MR analysis demonstrated causal effects of short sleep duration on CKD by the inverse variance weighted method, supported by causal estimates from MR-Egger regression. Conclusions These findings support an adverse effect of a short sleep duration on kidney function. Clinicians may encourage patients to avoid short-duration sleeping behavior to reduce CKD risk.
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“self-reported short or long sleep duration (often defined as <6 or 7 and >8 or 9 h, respectively) and poor sleep quality [Pittsburgh Sleep Quality Index (PSQI) > 5] may be consistently associated with adverse health outcomes”
From Sleep Duration/Quality with Health Outcomes: An Umbrella Review of Meta-Analyses of Prospective Studies (2022) · cites this paper as [3]
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A New Equation to Estimate Glomerular Filtration Rate
Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. (., Castro, A. F., Feldman, H. I., Kusek, J. W., Eggers, P., Van Lente, F., Greene, T., et al. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-9-200905050-00006 · Cited by 25,603
Sudlow, C., Gallacher, J., Allen, N., Beral, V., Burton, P., Danesh, J., Downey, P., Elliott, P., Green, J., Landray, M., et al. (2015) · PLOS Medicine · doi:10.1371/journal.pmed.1001779 · Cited by 12,728
Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015) · Gigascience · doi:10.1186/s13742-015-0047-8 · Cited by 12,709
Self-citationBowden, J., Davey Smith, G., & Burgess, S. (2015) · International Journal of Epidemiology · doi:10.1093/ije/dyv080 · Cited by 9,816
Bowden, J., Davey Smith, G., Haycock, P. C., & Burgess, S. (2016) · Genetic Epidemiology · doi:10.1002/gepi.21965 · Cited by 8,922
Bikbov, B. T., Purcell, C. A., Levey, A. S., Smith, M., Abdoli, A., Abebe, M., Adebayo, O., Afarideh, M., Agarwal, S. K., Agudelo‐Botero, M., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30045-3 · Cited by 7,131
Mendelian Randomization Analysis With Multiple Genetic Variants Using Summarized Data
Burgess, S., Butterworth, A., & Thompson, S. G. (2013) · Genetic Epidemiology · doi:10.1002/gepi.21758 · Cited by 6,050
(2010) · University of Twente Research Information · Cited by 6,037
Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians
Davies, N. M., Holmes, M. V., & Davey Smith, G. (2018) · BMJ · doi:10.1136/bmj.k601 · Cited by 4,404
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Mendelian Randomization Analysis as a Tool to Gain Insights into Causes of Diseases: A Primer
Tin, A., & Köttgen, A. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2020121760 · Cited by 118
Gao, C., Guo, J., Gong, T.-T., Lv, J.-L., Li, X.-Y., Liu, F.-H., Zhang, M., Shan, Y.-T., Zhao, Y.-H., & Wu, Q.-J. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.813943 · Cited by 88
“, short sleep and increased risk of hypertension (2), long sleep and increased risk of chronic kidney disease (3), poor sleep quality and increased risk of preterm birth (4), etc.”
BackgroundPark, S., Lee, S., Kim, Y., Cho, S., Kim, K., Kim, Y. C., Han, S. S., Lee, H., Lee, J. P., Joo, K. W., et al. (2021) · Kidney International · doi:10.1016/j.kint.2021.06.041 · Cited by 77
Adherence to a Healthy Sleep Pattern and Risk of Chronic Kidney Disease: The UK Biobank Study
Geng, T., Li, X., Ma, H., Heianza, Y., & Qi, L. (2022) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2021.08.028 · Cited by 73
Association Between Sleep Traits and Rheumatoid Arthritis: A Mendelian Randomization Study
Gao, R., Sang, N., Jia, C.-Z., Zhang, M.-Y., Li, B., Wei, M., & Wu, G. (2022) · Frontiers in Public Health · doi:10.3389/fpubh.2022.940161 · Cited by 71
Metadata
- Authors
- Park, S., Lee, S., Kim, Y., Lee, Y., Kang, M. W., Kim, K., Kim, Y. C., Han, S. S., Lee, H., Lee, J. P., Joo, K. W., Lim, C. S., Kim, Y. S., & Kim, D. K.
- Affiliations
- Seoul National University (KR)
- Seoul National University Hospital (KR)
- ORCID
- Venue
- Journal of the American Society of Nephrology
- Published
- 2020-10-01
- Volume
- 31
- Issue
- 12
- Pages
- 2937-2947
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- PMC
- PMC7790216
- OpenAlex
- W3090993883
- Cited by
- 123
- References
- 34
- Citations by year
- 2026: 5 · 2025: 27 · 2024: 24 · 2023: 24 · 2022: 24 · 2021: 16 · 2020: 3
- FWCI
- 16.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Ministry of Trade, Industry & Energy (10077474)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- short sleep duration, long sleep, chronic kidney disease, sleep duration, renal function, causal effects, polygenic risk score, sleep behavior, CKD stages 3-5, UK Biobank, genetic instruments, cardiovascular risk
- MeSH terms
- Adult, Aged, Female, United Kingdom, Humans, Male, Middle Aged, Sleep, Time Factors, Cohort Studies, Prevalence, Logistic Models, Odds Ratio, Renal Insufficiency, Chronic, Mendelian Randomization Analysis
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