Dataset Information

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

ABSTRACT: BACKGROUND AND PURPOSE:Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. METHODS:The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. RESULTS:Compared with normal sleep duration, long sleep (?9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. CONCLUSIONS:In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.

SUBMITTER: Titova OE

PROVIDER: S-EPMC7587241 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

Titova Olga E OE Michaëlsson Karl K Larsson Susanna C SC

Stroke 20200908 11

<h4>Background and purpose</h4>Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs.<h4>Methods</h4>The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up ...[more]

PMID: 32895015

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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.

Dataset Information

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

Publications

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

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