Dataset Information

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

ABSTRACT:

Objective

Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study.

Methods

In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and related genetic tools were used to search published genome-wide association studies for a two-sample Mendelian randomization (TSMR) analysis. The inverse-variance weighted (IVW) method was used as the main Mendelian randomization analysis method. Cochran's Q test was used to test heterogeneity, MR‒Egger was used to test horizontal pleiotropy, and the MR-PRESSO test was used to remove outliers.

Results

According to our research, insomnia (OR = 1.10, 95% CI 1.03-1.17, P = 2.59e-97), long sleep duration (OR = 0.66, 95% CI 0.37-1.17, P = 0.02), short sleep duration (OR = 1.30, 95% CI 1.22-1.38, P = 2.23e-17) and daytime sleepiness (OR = 1.49, 95% CI 1.25-1.77, P = 0.96e-4) had a bidirectional causal relationship with frailty.

Conclusions

Our research showed that there is a causal relationship between sleep disturbances and frailty. This result was obtained by a TSMR analysis, which involves the use of genetic variation as an IV to determine causal relationships between exposure and outcome. Future TSMR studies should include a larger sample for analysis.

SUBMITTER: Lu ZX

PROVIDER: S-EPMC10951186 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

Lu Zong-Xiao ZX Sang Ni N Liu Rong-Chao RC Li Bo-Han BH Zhang Meng-Yao MY Zhang Ming-Hui MH Cheng Meng-Cheng MC Wu Guo-Cui GC

European journal of ageing 20240319 1

<h4>Objective</h4>Adequate sleep is closely related to people's health. However, with increasing age, the quality of sleep worsens. At the same time, among elderly individuals, frailty is also a disturbing factor, which makes elderly individuals more vulnerable to negative factors. To explore the relationship between the two, we conducted this study.<h4>Methods</h4>In this paper, independent genetic variations related to insomnia, sleep duration and daytime sleepiness were selected as IVs, and r ...[more]

PMID: 38502408

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Project description:IntroductionSleep is associated with psychiatric disorders. However, their causality remains unknown.MethodsThe study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran's Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis.ResultsInsomnia (OR = 2.02, 95%CI = 1.34-3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34-2.44, FDR corrected p-value<0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24-3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20-16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11-4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42-0.93, FDR corrected p-value = 0.088).ConclusionThis study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.

Project description:Background Previous observational studies have shown that low back pain (LBP) often coexists with sleep disturbances, however, the causal relationship remains unclear. In the present study, the causal relationship between sleep disturbances and LBP was investigated and the importance of sleep improvement in the comprehensive management of LBP was emphasized. Methods Genetic variants were extracted as instrumental variables (IVs) from the genome-wide association study (GWAS) of insomnia, sleep duration, short sleep duration, long sleep duration, and daytime sleepiness. Information regarding genetic variants in LBP was selected from a GWAS dataset and included 13,178 cases and 164,682 controls. MR-Egger, weighted median, inverse-variance weighted (IVW), penalized weighted median, and maximum likelihood (ML) were applied to assess the causal effects. Cochran’s Q test and MR-Egger intercept were performed to estimate the heterogeneity and horizontal pleiotropy, respectively. Outliers were identified and eliminated based on MR-PRESSO analysis to reduce the effect of horizontal pleiotropy on the results. Removing each genetic variant using the leave-one-out analysis can help evaluate the stability of results. Finally, the reverse causal inference involving five sleep traits was implemented. Results A causal relationship was observed between insomnia-LBP (OR = 1.954, 95% CI: 1.119–3.411), LBP-daytime sleepiness (OR = 1.011, 95% CI: 1.004–1.017), and LBP-insomnia (OR = 1.015, 95% CI: 1.004–1.026), however, the results of bidirectional MR analysis between other sleep traits and LBP were negative. The results of most heterogeneity tests were stable and specific evidence was not found to support the disturbance of horizontal multiplicity. Only one outlier was identified based on MR-PRESSO analysis. Conclusion The main results of our research showed a potential bidirectional causal association of genetically predicted insomnia with LBP. Sleep improvement may be important in comprehensive management of LBP.

Project description:BackgroundA potential link between asthma and frailty has been suggested in previous studies. However, the nature of the causal relationship between these two conditions warrants further investigation. Therefore, this study assessed the bidirectional causality between asthma and frailty risk using two-sample Mendelian randomization (MR).MethodsThe study data were obtained from the genome-wide association study (GWAS) dataset, with 337,159 samples representing asthma data and 175,226 samples representing frailty. The causal relationship between the two disorders was assessed by selecting the single nucleotide polymorphisms (SNPs), significantly associated with both asthma and frailty. The inverse variance weighting (IVW) method was used as the main analytical method to estimate the possible influence of causality. Sensitivity analysis was also performed using Mr-Egger intercept, funnel plot, "leave-one-out," and Cochran Q test. In addition, potential mediators were investigated by risk factor analysis.ResultThe IVW method showed an increased risk of frailty due to increased genetic susceptibility factors and the number of to asthma (OR = 2.325, 95%CI:1.958-2.761; p = 6.527498e-22), while no horizontal pleiotropy was observed for the Mr-Egger intercept (p = 0.609) and the funnel plot. The Cochran Q value was 72.858, p = 0.024, and there was heterogeneity in the Cochran Q-value. No single SNP was observed for "leave-one-out" that had a biasing effect on the instrumental variables. In addition, genetic susceptibility to frailty was associated with asthma (OR = 1.088, 95%CI:1.058-1.119; p = 4.815589e-09). In the causal relationship described above, several risk factors for frailty are complex, with asthma leading to a significant reduction in physical activity endurance.ConclusionOur findings suggest a probable positive causal effect of asthma on the risk of developing frailty, potentially mediated by reduced physical activity endurance. At the same time, a causal relationship exists between frailty and asthma. Therefore, assessment strategies for frailty should include asthma and vice versa.

Dataset Information

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

Objective

Methods

Results

Conclusions

Publications

The causal relationship between sleep disturbances and the risk of frailty: a two-sample Mendelian randomization study.

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