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The relationship between sleep duration, cognition and dementia: a Mendelian randomization study.

ABSTRACT: BACKGROUND:Short and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal. METHODS:We conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N?=?395?803) and summary statistics from the International Genomics of Alzheimer's Project (N cases/controls?=?17?008/37?154) to investigate the potential impact of sleep duration on cognitive outcomes. RESULTS:Linear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI)?=?0-2%; P?=?0.008] slower reaction time and 3% more errors in visual-memory test (95% CI?=?0-6%; P?=?0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep?=?1.10 (95% CI?=?0.76-1.57); P?=?0.62], decline in reaction time [OR?=?1.28 (95% CI?=?0.49-3.35); P?=?0.61], all-cause dementia [OR?=?1.19 (95% CI?=?0.65-2.19); P?=?0.57] or Alzheimer's disease risk [OR?=?0.89 (95% CI?=?0.67-1.18); P?=?0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity?=?3.44e-9) and reaction time (P for non-linearity?=?6.66e-16). CONCLUSIONS:Linear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition.

SUBMITTER: Henry A

PROVIDER: S-EPMC6659373 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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The relationship between sleep duration, cognition and dementia: a Mendelian randomization study.

Henry Albert A Katsoulis Michail M Masi Stefano S Fatemifar Ghazaleh G Denaxas Spiros S Acosta Dionisio D Garfield Victoria V Dale Caroline E CE

International journal of epidemiology 20190601 3

<h4>Background</h4>Short and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.<h4>Methods</h4>We conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N = 395 803) and summary statistics from the International Genomics of Alzheimer's Project (N cases/controls = 17 008/37 154) to investigat ...[more]

PMID: 31062029

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Project description:ObjectiveObservational research has indicated a potential link between dietary salt intake and susceptibility to dementia. However, it is important to note that these types of studies are prone to the issues of reverse causation and residual confounding. Therefore, we conducted a two-sample Mendelian randomization (MR) study to explore the causality.MethodTo explore the causal relationship between them, this Mendelian randomization (MR) study incorporated summary statistics of dietary salt intake and dementia. We estimated the causality between salt intake and the risk of overall dementia and various subtypes of dementia, including Alzheimer's disease (AD), Vascular dementia (VaD), and Lewy body dementia (LBD). The inverse variance-weighted (IVW) method was the major MR analysis. To conduct sensitivity analyses, we employed various MR methods, the pleiotropy residual sum and outlier (MR-PRESSO) method, and the leave-one-out approach. The MR-Egger intercept and Cochran's Q test were conducted to test pleiotropy and heterogeneity respectively.ResultsA suggestive association was observed for genetically predicted higher dietary salt intake and increased risk of overall dementia in the European ancestry [odds ratio (OR): 1.542; 95% confidence interval (95% CI): 1.095-2.169; P = 0.013]. The causal relationship between dietary salt intake and overall dementia is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Meanwhile, no clear heterogeneity or pleiotropy was identified. However, we failed to detect a causal effect of dietary salt intake on the risk of various dementia subtypes.ConclusionThe results of this research present strong evidence that established a significant association between dietary salt intake and the likelihood of developing dementia. These findings reinforce the notion that the amount of dietary salt intake plays a crucial role in determining the risk of acquiring this cognitive condition. By establishing a definitive correlation, this study highlights the importance of reducing salt consumption as a preventive measure against dementia.

Project description:ObjectivesExtensive researches highlight the detrimental impact of sleep disorders such as insomnia and insufficient sleep duration on kidney function. However, establishing a clear causal relationship between insomnia, sleep duration, and kidney function remains challenging. This study aims to estimate this relationship using Mendelian randomization (MR).MethodsIndependent genetic variants strongly associated with insomnia (N = 462,341) and sleep duration (N = 460,099) were selected as instrumental variables from corresponding genome-wide association studies (GWAS). Kidney function parameters, including serum creatinine, estimated glomerular filtration rate by cystatin C (eGFRcys), acute renal failure (ARF), chronic renal failure (CRF), kidney injury molecule-1, neutrophil gelatinase associated lipocalin, microalbuminuria, cystatin C, and β2 microglobulin, were derived from GWAS databases. A two-sample MR study was conducted to assess the causal relationship between sleep disorders and kidney function, and multivariable MR was used to identify potential mediators. The inverse-variance weighted was used as the primary estimate.ResultsMR analysis found robust evidence indicating that insomnia and short sleep duration were associated with an increased risk of elevated serum creatinine, regardless of adjusting for obesity. Causal links between sleep duration and eGFRcys or cystatin C were also identified. While genetically predicted insomnia and sleep duration were found to potentially impact ARF, CRF, microalbuminuria, and β2 microglobulin, the p-values in multivariable MR analysis became nonsignificant. No pleiotropy was detected.ConclusionsThis study demonstrates a causal impact of insomnia on the risk of elevated serum creatinine and a positive effect of sleep duration on serum creatinine, eGFRcys, and cystatin C. Our findings also suggest their potential indirect effects on ARF, CRF, microalbuminuria, and β2 microglobulin mediated by obesity.

Project description:BackgroundChronic inadequate sleep and frequent daytime napping may inflict deleterious health effects including weight gain, cardiometabolic and psychiatric diseases, and cancer. It is plausible that these relations may be partly influenced by the consumption of suboptimal diets.ObjectivesThe study aimed to identify potential causal links of genetically proxied longer habitual sleep duration and more frequent daytime napping on 61 dietary variables derived from an FFQ. In addition, the study aimed to assess potential bidirectional causal links between habitual sleep duration or daytime napping and macronutrient composition.MethodsGenetic variants robustly associated with habitual sleep duration and daytime napping from published genome-wide association analyses were used. Outcomes included 61 dietary variables estimated from FFQs in the UK Biobank (n = 361,194). For bidirectional associations with macronutrient composition, genetic variants associated with percentage of energy from carbohydrate, fat, and protein were used. Two-sample Mendelian randomization (MR) effects were estimated with inverse-variance weighted (IVW) analysis.ResultsIn 2-sample MR, genetically proxied longer sleep duration was associated with a 0.068 (95% CI: 0.034, 0.103) category increase in salad/raw vegetable intake [P false discovery rate (FDR) = 0.006] per hour of sleep and with "no major dietary changes in the past 5 years" (P FDR = 0.043). No associations were evident for daytime napping on dietary variables (all P FDR > 0.05). In addition, there were no bidirectional associations between habitual sleep duration or daytime napping with the relative intake of carbohydrate, fat, and protein (all P IVW > 0.05).ConclusionsIn this MR study, there was modest evidence for associations between habitual sleep duration with dietary intake and no evidence for associations between daytime napping frequency with dietary intake. These preliminary findings suggest that changes to habitual sleep duration or daytime napping frequency may have limited impact on long-term changes in dietary intake.

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The relationship between sleep duration, cognition and dementia: a Mendelian randomization study.

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The relationship between sleep duration, cognition and dementia: a Mendelian randomization study.

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