Short or Long Sleep Duration and CKD: A Mendelian Randomization Study

Sehoon Park 1 2, Soojin Lee 3 4, Yaerim Kim 5, Yeonhee Lee 3 4, Min Woo Kang 3 4, Kwangsoo Kim 6, Yong Chul Kim 3, Seung Seok Han 3 7, Hajeong Lee 3, Jung Pyo Lee 3 7 8, Kwon Wook Joo 3 4 7, Chun Soo Lim 3 7 8, Yon Su Kim 1 3 4 7, Dong Ki Kim 9 4 7

Affiliations

PMID: 33004418
DOI: 10.1681/ASN.2020050666

Abstract

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.

Keywords: Mendelian randomization; chronic kidney disease; end-stage kidney disease; genetic risk score; sleep.