Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

Serum selenium levels are inversely associated with death risk among hemodialysis patients.

BACKGROUND: Previous studies have indicated that serum selenium levels are decreased in hemodialysis patients. Selenium deficiency may contribute to an increased risk for death among hemodialysis patients. METHODS: A population-based prospective cohort study in adult hemodialysis patients was conducted. A total of 1041 patients were enrolled. Patients were divided into quartile groups according to serum selenium levels. Mortality rates between the groups were compared by the log-rank test. Associations between serum selenium levels and cause-specific mortality risks in hemodialysis patients were examined by Cox's regression model. RESULTS: A total of 382 patients died during the 5-year follow-up period (median follow-up period, 4.9 years). Crude mortality rates in quartile groups according to serum selenium levels were 134.5, 99.9, 85.9 and 55.2 (per 1000 patient-years), respectively. The lowest quartile group had significantly higher mortality rates from all-cause and infectious disease-related death than the rates in the other three groups (P < 0.001, by log-rank test). Mortality rates from cardiovascular and malignant disease-related death were similar between the groups. A strong inverse relationship between selenium levels and infectious disease-related death was observed even after multivariate adjustment (trend P = 0.024). CONCLUSIONS: Serum selenium levels were inversely associated with death risk, especially death risk due to infectious disease, among hemodialysis patients. Decreased serum selenium level may contribute to immunity dysfunction and may increase the risk of death from infectious disease in hemodialysis patients.

Serum selenium levels in hemodialysis patients are significantly lower than those in healthy controls.

Serum selenium levels have been thought to be decreased in hemodialysis patients; however, results of previous studies have been inconsistent. Population-based hemodialysis patients (n = 1,041) and randomly recruited healthy controls (n = 384) were enrolled. Serum selenium levels were determined by inductively coupled plasma mass spectrometry and compared in hemodialysis patients and controls using analysis of covariance after adjustment for confounding factors with p < 0.1 as the result of the multiple regression analysis. Age, serum albumin levels, hsCRP levels, LDLC levels, HDLC levels, regular drinking habit and hemodialysis treatment were significantly associated with serum selenium levels in multiple regression analysis. Multivariate-adjusted means (95% CIs) of serum selenium levels were 103 µg/l (101-105) in hemodialysis patients and 117 µg/l (114-121) in controls. Selenium levels in hemodialysis patients were decreased. Whether decreased serum selenium levels contribute to increased risks for morbidity and mortality in hemodialysis patients should be examined.