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

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.