Polygenic score for sleep duration. Association with cognition.
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ABSTRACT: Study objectives
Age-related changes in sleep include a reduction in total sleep time and a greater incidence of sleep disorders, and are also an integral part of neurodegenerations. In the present study, we aimed to: a) identify common genetic variants that may influence self-reported sleep duration, and b) examine the association between the identified genetic variants and performance in different cognitive domains.Methods
A sample of 197 cognitively healthy participants, aged 20-80 years, mostly non-Hispanic Whites (69%), were selected from the Reference Abilities Neural Network and the Cognitive Reserve study. Each participant underwent an evaluation of sleep function and assessment of neuropsychological performance on global cognition and four different domains (memory, speed of processing, fluid reasoning, language). Published GWAS summary statistics from a Polygenic Score (PS) for sleep duration in a large European ancestry cohort (N = 30,251) were used to derive a PS in our study sample. Multivariate linear models were used to test the associations between the PS and sleep duration and cognitive performance. Age, sex, and education were used as covariates. Secondary analyses were conducted in three age-groups (young, middle, old).Results
Higher PS was linked to longer sleep duration and was also associated with better performance in global cognition, fluid reasoning, speed of processing, and language, but not memory. Results especially for fluid reasoning, language, and global cognition were driven mostly by the young group.Conclusions
Our study replicated the previously reported association between sleep-PS and longer sleep duration. We additionally found a significant association between the sleep-PS and cognitive function. Our results suggest that common genetic variants may influence the link between sleep duration and cognitive health.
SUBMITTER: Tsapanou A
PROVIDER: S-EPMC7541541 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6424085 | biostudies-literature
Project description:ImportanceDisrupted sleep is common in aging and is associated with cognition. Age-related changes to sleep are associated with multiple causes, including early Alzheimer disease pathology (amyloid β [Aβ]), depression, and cardiovascular disease.ObjectiveTo investigate the associations between self-reported sleep duration and brain Aβ burden as well as the demographic, cognitive, and lifestyle variables in adults with normal cognition.Design, setting, and participantsThis cross-sectional study obtained data from participants in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study, which is being conducted in 67 sites in the United States, Canada, Australia, and Japan. The sample for this analysis consisted of individuals aged 65 to 85 years who underwent an Aβ positron emission tomography (PET) scan, had complete apolipoprotein E (APOE) genotype data, and were identified as clinically normal (per a Clinical Dementia Rating score of 0) and cognitively unimpaired (per a Mini-Mental State Examination score of 25 to 30 and Logical Memory Delayed Recall test score of 6 to 18). Data were analyzed from April 3, 2020, to June 20, 2021.Main outcomes and measuresThe outcome was self-reported nightly sleep duration (grouped by short sleep duration: ≤6 hours, normal sleep duration: 7-8 hours, and long sleep duration: ≥9 hours) compared with demographic characteristics, Aβ burden (as measured with a fluorine 18-labeled-florbetapir PET scan), objective and subjective cognitive function measures, and lifestyle variables.ResultsThe 4417 participants in the study included 2618 women (59%) and had a mean (SD) age of 71.3 (4.7) years. Self-reported shorter sleep duration was linearly associated with higher Aβ burden (β [SE] = -0.01 [0.00]; P = .005), and short sleep duration was associated with reduced cognition that was mostly in memory domains. No difference in Aβ was found between long and normal sleep duration groups (β [SE] = 0.00 [0.01]; P = .99). However, compared with normal sleep duration, both short and long sleep durations were associated with higher body mass index (short vs normal sleep duration: β [SE] = 0.48 [0.17], P = .01; long vs normal sleep duration: β [SE] = 0.97 [0.31], P = .002), depressive symptoms (short vs normal sleep duration: β [SE] = 0.31 [0.05], P < .001; long vs normal sleep duration: β [SE] = 0.39 [0.09], P < .001), and daytime napping (short vs normal sleep duration: β [SE] = 2.66 [0.77], P = .001; long vs normal sleep duration: β [SE] = 3.62 [1.38], P = .01). Long sleep duration was associated with worse performance across multiple cognitive domains.Conclusions and relevanceIn this cross-sectional study, both short and long sleep durations were associated with worse outcomes for older adults, such as greater Aβ burden, greater depressive symptoms, higher body mass index, and cognitive decline, emphasizing the importance of maintaining adequate sleep.
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Project description:Interventions: Case group:N/A;Control group:N/A
Primary outcome(s): Group odds ratio;95% confidence interval
Study Design: Case-Control study
| 82240 | ecrin-mdr-crc
Project description:Importance:Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives:To examine whether genetic information alone can identify children at risk of myopia development and whether including a child's genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants:Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures:The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to -0.75 diopter (D) (any), less than or equal to -3.00 D (moderate), or less than or equal to -5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n?=?95?619), age of onset of spectacle wear (n?=?287?448), and educational attainment (n?=?328?917). Results:A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P?=?.02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4-10.9) of high myopia. Conclusions and Relevance:A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87).
| S-EPMC6824229 | biostudies-literature
Project description:ImportanceAn association between sleep duration and the trajectory of cognitive decline has not been conclusively demonstrated.ObjectiveTo investigate the association between sleep duration and cognitive decline by a pooled analysis of 2 nationally representative aging cohorts.Design, setting, and participantsA pooled cohort study using data from waves 4 to 8 (2008-2009 to 2016-2017) in the English Longitudinal Study of Ageing and waves 1 to 3 (2011 to 2015) in the China Health and Retirement Longitudinal Study in a population-based setting. Participants were 2 randomly enrolled cohorts comprising 28 756 individuals living in England who were 50 years or older and those living in China who were 45 years or older.ExposureSelf-reported sleep duration per night according to face-to-face interviews.Main outcomes and measuresGlobal cognitive z scores were calculated according to immediate and delayed recall test, an animal fluency test, the serial sevens test, an intersecting pentagon copying test, and a date orientation test.ResultsData were analyzed from 20 065 participants, including 9254 from the English Longitudinal Study of Ageing (mean [SD] age, 64.6 [9.8] years; 55.9% [5174 of 9254] women; median follow-up duration, 8 [interquartile range, 6-8] years) and 10 811 from the China Health and Retirement Longitudinal Study (mean [SD] age, 57.8 [9.0] years; 50.2% [5425 of 10 811] men; median follow-up duration, 4 [interquartile range, 4-4] years). During 100 000 person-years of follow-up, global cognitive z scores in individuals with 4 hours or less (pooled β = -0.022; 95% CI, -0.035 to -0.009 SD per year; P = .001) and 10 hours or more (pooled β = -0.033; 95% CI, -0.054 to -0.011 SD per year; P = .003) of sleep per night declined faster than in the reference group (7 hours per night) after adjusting for a number of covariates. An inverted U-shaped association between sleep duration and global cognitive decline was also observed.Conclusions and relevanceIn this pooled cohort study, an inverted U-shaped association between sleep duration and global cognitive decline was found, indicating that cognitive function should be monitored in individuals with insufficient (≤4 hours per night) or excessive (≥10 hours per night) sleep duration. Future studies are needed to examine the mechanisms of the association between sleep duration and cognitive decline.
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Project description:BACKGROUND:Short sleep may be a risk factor for atrial fibrillation. However, previous investigations have been limited by lack of objective sleep measurement and small sample size. We sought to determine the association between objectively measured sleep duration and atrial fibrillation. METHODS:All 31,079 adult patients undergoing diagnostic polysomnography from 1999 to 2015 at multiple sites within a large hospital network were identified from electronic medical records. Prevalent atrial fibrillation was identified by continuous ECG during polysomnography. Incident atrial fibrillation was identified by diagnostic codes and 12-lead ECGs. Logistic regression and Cox proportional hazards modeling were used to examine the association of sleep duration and atrial fibrillation prevalence and incidence, respectively, adjusting for age, sex, BMI, hypertension, coronary artery disease, cerebrovascular disease, peripheral vascular disease, heart failure, and sleep apnea severity. RESULTS:We identified 404 cases of prevalent atrial fibrillation among 30,061 individuals (mean age ± SD, 51.0 ± 14.5 years; 51.6% women) undergoing polysomnography. After adjustment, each 1-h reduction in sleep duration was associated with a 1.17-fold (95% CI, 1.11-1.30) increased risk of prevalent atrial fibrillation. Among 27,589 patients without atrial fibrillation at baseline, we identified 1,820 cases of incident atrial fibrillation over 4.6 years median follow-up. After adjustment, each 1-h reduction in sleep duration was associated with a 1.09-fold (95% CI, 1.05-1.13) increased risk for incident atrial fibrillation. CONCLUSIONS:Short sleep duration is independently associated with prevalent and incident atrial fibrillation. Further research is needed to determine whether interventions to extend sleep can lower atrial fibrillation risk.
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