scholarly journals The impact of Mendelian sleep and circadian genetic variants in a population setting

2022 ◽  
Author(s):  
Michael N Weedon ◽  
Samuel E Jones ◽  
Jacqueline Lane ◽  
Jiwon Lee ◽  
Hanna M Ollila ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Rare Variants ◽  
Sequence Data ◽  
Large Population ◽  
Population Based ◽  
Self Report ◽  
Uk Biobank ◽  
Sleep Phase ◽  
Sleep Timing ◽  
The Impact

Rare variants in ten genes have been reported to cause Mendelian sleep conditions characterised by extreme sleep duration or timing. These include familial natural short sleep (ADRB1, DEC2/BHLHE41, GRM1 and NPSR1), advanced sleep phase (PER2, PER3, CRY2, CSNK1D and TIMELESS) and delayed sleep phase (CRY1). The association of variants of these genes with extreme sleep conditions were usually based on clinically ascertained families, and their effects when identified in the population are unknown. We aimed to determine the effects of these variants on sleep traits in large population-based cohorts. We performed genetic association analysis of variants previously reported to be causal for Mendelian sleep and circadian conditions. Analyses were performed using 191,929 individuals with data on sleep and whole-exome or genome-sequence data from 4 population-based studies: UK Biobank, FINRISK, Health-2000-2001, and the Multi-Ethnic Study of Atherosclerosis (MESA). We identified sleep disorders from self-report, hospital and primary care data. We estimated sleep duration and timing measures from self-report and accelerometery data. We identified carriers for 10 out of 12 previously reported pathogenic variants for 8 of the 10 genes. They ranged in frequency from 1 individual with the variant in CSNK1D to 1,574 individuals with a reported variant in the PER3 gene in the UK Biobank. We found no association of any of these variants with extreme sleep or circadian phenotypes. Using sleep timing as a proxy measure for sleep phase, only PER3 and CRY1 variants demonstrated association with earlier and later sleep timing, respectively; however, the magnitude of effect was smaller than previously reported (sleep midpoint ~7 mins earlier and ~5 mins later, respectively). We also performed burden tests of protein truncating (PTVs) or rare missense variants for the 10 genes. Only PTVs in PER2 and PER3 were associated with a relevant trait (for example, 64 individuals with a PTV in PER2 had an odds ratio of 4.4 for being "definitely a morning person", P=4x10-8; and had a 57-minute earlier midpoint sleep, P=5x10-7). Our results indicate that previously reported variants for Mendelian sleep and circadian conditions are often not highly penetrant when ascertained incidentally from the general population.

scholarly journals Analysis of 50,000 exome-sequenced UK Biobank subjects fails to identify genes influencing probability of psychiatric referral

2020 ◽  
Author(s):  
David Curtis
Keyword(s):  
Multiple Testing ◽  
Rare Variants ◽  
Sequence Data ◽  
Statistical Significance ◽  
Major Effect ◽  
Self Report ◽  
Uk Biobank ◽  
Functional Variants ◽  
Exome Sequence Data ◽  
Exome Sequence

Background Depression is moderately heritable but there is no common genetic variant which has a major effect on susceptibility. It is possible that some very rare variants could have substantial effect sizes and these could be identified from exome sequence data. Methods Data from 50,000 exome-sequenced UK Biobank participants was analysed. Subjects were treated as cases if they had reported having seen a psychiatrist for "nerves, anxiety, tension or depression". Gene-wise weighted burden analysis was performed to see if there were any genes or sets of genes for which there was an excess of rare, functional variants in cases. Results There were 5,872 cases and 43,862 controls. There were 22,028 informative genes but none produced a statistically significant result after correction for multiple testing. Of the 25 genes individually significant at p<0.001 none appeared to be a biologically plausible candidate. No set of genes achieved statistical significance after correction for multiple testing and those with the lowest p values again did not appear to be biologically plausible candidates. Limitations The phenotype is based on self-report and the cases are likely to somewhat heterogeneous. The number of cases is on the low side for a study of exome sequence data. Conclusions The results conform exactly with the expectation under the null hypothesis. It seems unlikely that depression genetics research will produce findings that might have a substantial clinical impact until far larger samples become available.

Effects of Quarantine Due to the COVID-19 on Sleep Duration and Quality in Algerians

2020 ◽  
Vol 60 (2) ◽  
pp. 182-193
Author(s):  
Kacem Abdelhadi ◽  
Houar Abdelatif ◽  
Zerf Mohamed ◽  
Bengoua Ali
Keyword(s):  
Statistical Analysis ◽  
Sleep Quality ◽  
Sleep Duration ◽  
Online Survey ◽  
Public Awareness ◽  
Italian Version ◽  
Sleep Timing ◽  
Algerian Population ◽  
Significant Change ◽  
The Impact

SummaryThis study tests the impact of COVID-19 on sleep of Algerian population before and during the COVID-19 quarantine by an estimated online survey, adapted from the PSQI Italian version. Including 1210 participants (age between 18-60 years old). The statistical analysis was carried out using SPSS version 22.0 software. Our results showed a significant change in sleeping quality during quarantine, the sleep timing markedly changed, we also noticed additional use of sleeping medications. Algerian scientists recommend to build public awareness and to provide necessary information regarding Algerian sleep quality, especially for Algerian adults.

scholarly journals 699 Sleep Health Traits and COVID-19: Mortality Risk from the UK Biobank

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu
Keyword(s):  
Risk Factors ◽  
Sleep Apnea ◽  
Sleep Duration ◽  
Sex Education ◽  
Mortality Risk ◽  
Self Report ◽  
Severe Illness ◽  
Uk Biobank ◽  
Sleep Health ◽  
The Uk

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (&gt;9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.

scholarly journals Primary Care Consultations after Hospitalisation for Pneumonia: A Large Population-based Cohort Study

2020 ◽  
pp. BJGP.2020.0890
Author(s):  
Vadsala Baskaran ◽  
Fiona Pearce ◽  
Rowan H Harwood ◽  
Tricia McKeever ◽  
Wei Shen Lim
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Large Population ◽  
Significant Proportion ◽  
Antibiotic Use ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Respiratory Disorder ◽  
The Impact

Background: Up to 70% of patients report ongoing symptoms four weeks after hospitalisation for pneumonia, and the impact on primary care is poorly understood. Aim: To investigate the frequency of primary care consultations after hospitalisation for pneumonia, and the reasons for consultation. Design: Population-based cohort study. Setting: UK primary care database of anonymised medical records (Clinical Practice Research Datalink, CPRD) linked to Hospital Episode Statistics (HES), England. Methods: Adults with the first ICD-10 code for pneumonia (J12-J18) recorded in HES between July 2002-June 2017 were included. Primary care consultation within 30 days of discharge was identified as the recording of any medical Read code (excluding administration-related codes) in CPRD. Competing-risks regression analyses were conducted to determine the predictors of consultation and antibiotic use at consultation; death and readmission were competing events. Reasons for consultation were examined. Results: Of 56,396 adults, 55.9% (n=31,542) consulted primary care within 30 days of discharge. The rate of consultation was highest within 7 days (4.7 per 100 person-days). The strongest predictor for consultation was a higher number of primary care consultations in the year prior to index admission (adjusted sHR 8.98, 95% CI 6.42-12.55). The commonest reason for consultation was for a respiratory disorder (40.7%, n=12,840), 12% for pneumonia specifically. At consultation, 31.1% (n=9,823) received further antibiotics. Penicillins (41.6%, n=5,753) and macrolides (21.9%, n=3,029) were the commonest antibiotics prescribed. Conclusion: Following hospitalisation for pneumonia, a significant proportion of patients consulted primary care within 30 days, highlighting the morbidity experienced by patients during recovery from pneumonia.

scholarly journals Analysis of exome-sequenced UK Biobank subjects implicates genes affecting risk of hyperlipidaemia

2020 ◽  
Author(s):  
David Curtis
Keyword(s):  
Rare Variants ◽  
Sequence Data ◽  
Lipid Lowering ◽  
P Value ◽  
Data Sets ◽  
Uk Biobank ◽  
Functional Studies ◽  
Exome Sequence Data ◽  
Rare Genetic Variants ◽  
The Uk

Rare genetic variants in LDLR, APOB and PCSK9 are known causes of familial hypercholesterolaemia and it is expected that rare variants in other genes will also have effects on hyperlipidaemia risk although such genes remain to be identified. The UK Biobank consists of a sample of 500,000 volunteers and exome sequence data is available for 50,000 of them. 11,490 of these were classified as hyperlipidaemia cases on the basis of having a relevant diagnosis recorded and/or taking lipid-lowering medication while the remaining 38,463 were treated as controls. Variants in each gene were assigned weights according to rarity and predicted impact and overall weighted burden scores were compared between cases and controls, including population principal components as covariates. One biologically plausible gene, HUWE1, produced statistically significant evidence for association after correction for testing 22,028 genes with a signed log10 p value (SLP) of -6.15, suggesting a protective effect of variants in this gene. Other genes with uncorrected p<0.001 are arguably also of interest, including LDLR (SLP=3.67), RBP2 (SLP=3.14), NPFFR1 (SLP=3.02) and ACOT9 (SLP=-3.19). Gene set analysis indicated that rare variants in genes involved in metabolism and energy can influence hyperlipidaemia risk. Overall, the results provide some leads which might be followed up with functional studies and which could be tested in additional data sets as these become available. This research has been conducted using the UK Biobank Resource.

scholarly journals Occupations associated with COPD risk in the large population-based UK Biobank cohort study

2016 ◽  
Vol 73 (6) ◽  
pp. 378-384 ◽  
Author(s):  
Sara De Matteis ◽  
Deborah Jarvis ◽  
Sally Hutchings ◽  
Andy Darnton ◽  
David Fishwick ◽  
...  
Keyword(s):  
Cohort Study ◽  
Large Population ◽  
Population Based ◽  
Uk Biobank

Consecutive Days of Racing Does Not Affect Sleep in Professional Road Cyclists

2021 ◽  
pp. 1-4
Author(s):  
Charli Sargent ◽  
Shona L. Halson ◽  
David T. Martin ◽  
Gregory D. Roach
Keyword(s):  
Sleep Duration ◽  
Sleep Onset ◽  
Self Report ◽  
Activity Monitors ◽  
Sleep Diaries ◽  
Time In Bed ◽  
Road Cycling ◽  
Offset Time ◽  
The Impact

Purpose: Professional road cycling races are physiologically demanding, involving successive days of racing over 1 to 3 weeks of competition. Anecdotal evidence indicates that cyclists’ sleep duration either increases or deteriorates during these competitions. However, sleep duration in professional cyclists during stage races has not been assessed. This study examined the amount/quality of sleep obtained by 14 professional cyclists competing in the Australian Tour Down Under. Methods: Sleep was assessed using wrist activity monitors and self-report sleep diaries on the night prior to start of the race and on each night during the race. The impact of each day of the race on sleep onset, sleep offset, time in bed, sleep duration, and wake duration was assessed using separate linear mixed effects models. Results: During the race, cyclists obtained an average of 6.8 (0.9) hours of sleep between 23:30 and 07:27 hours and spent 13.9% (4.7%) of time in bed awake. Minor differences in sleep onset (P = .023) and offset times (P ≤.001) were observed during the week of racing, but these did not affect the amount of sleep obtained by cyclists. Interestingly, the 3 best finishers in the general classification obtained more sleep than the 3 worst finishers (7.2 [0.3] vs 6.7 [0.3] h; P = .049). Conclusions: Contrary to anecdotal reports, the amount of sleep obtained by cyclists did not change over the course of the 1-week race and was just below the recommended target of 7 to 9 hours for adults.

scholarly journals Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 672-683 ◽  
Author(s):  
Todd Smith ◽  
David C Muller ◽  
Karel G M Moons ◽  
Amanda J Cross ◽  
Mattias Johansson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Prediction Models ◽  
Large Population ◽  
External Validation ◽  
Population Based ◽  
Prognostic Models ◽  
Uk Biobank ◽  
Asymptomatic Individuals ◽  
The Uk

ObjectiveTo systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DesignModels were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).ResultsThe systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC.ConclusionSeveral of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.

Critical appraisal of a large population-based case–control study

2017 ◽  
Author(s):  
Mark Elwood
Keyword(s):  
Dose Response ◽  
Case Control Study ◽  
Large Population ◽  
Quantitative Relationship ◽  
Population Based ◽  
Case Control ◽  
Critical Assessment ◽  
Response Consistency ◽  
The Impact ◽  
Control Study

This chapter shows a large population-based case-control study, to address the quantitative relationship between alcohol consumption and breast cancer. It shows the logistic and design issues, and the assessment of dose-response, consistency and specificity. The critical assessment follows the scheme set out in chapter 10: describing the study, assessing the non-causal explanations of observation bias, confounding, and chance variation; assessing time relationships, strength, dose-response, consistency and specificity, and applying the results to the eligible, source, and target populations; and then comparing the results with evidence from other studies, considering consistency and specificity, biological mechanisms, and coherence with the distribution of exposures and outcomes. The chapter gives a summary and table of the critical assessment and its conclusions; and comments on the impact of the study and research carried out since.

Sign in / Sign up

Export Citation Format

Share Document