scholarly journals Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study

SLEEP ◽  
2022 ◽  
Author(s):  
Zheran Liu ◽  
Yaxin Luo ◽  
Yonglin Su ◽  
Zhigong Wei ◽  
Ruidan Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
Mendelian Randomization ◽  
Causal Link ◽  
Uk Biobank ◽  
Inverse Variance ◽  
Increased Risk ◽  
Weighted Median ◽  
The Uk

Abstract Study Objectives Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. Methods Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomization (MR) analyses were conducted to estimate the causal effects of the significant findings in the observation analyses. Beta values and the corresponding 95% CIs were calculated and compared using the inverse variance weighting, weighted median, and MR-Egger methods. Results In the UK Biobank cohort study, both often excessive daytime sleepiness and sometimes daytime napping were associated with hospitalized COVID-19 (excessive daytime sleepiness [often vs. never]: RR=1.24, 95% CI=1.02-1.5; daytime napping [sometimes vs. never]: RR=1.12, 95% CI=1.02-1.22). In addition, sometimes daytime napping was also associated with an increased risk of COVID-19 susceptibility (sometimes vs. never: RR= 1.04, 95% CI=1.01-1.28). In the MR analyses, excessive daytime sleepiness was found to increase the risk of hospitalized COVID-19 (MR IVW method: OR = 4.53, 95% CI = 1.04-19.82), whereas little evidence supported a causal link between daytime napping and COVID-19 outcomes. Conclusions Observational and genetic evidence supports a potential causal link between excessive daytime sleepiness and an increased risk of COVID-19 hospitalization, suggesting that interventions targeting excessive daytime sleepiness symptoms might decrease severe COVID-19 rate.

Daytime sleepiness, night sleep changes and ALS: a Mendelian randomization study

2020 ◽  
Author(s):  
Gan Zhang ◽  
Linjing Zhang ◽  
Tao Huang ◽  
Dongsheng Fan
Keyword(s):  
Sleep Duration ◽  
Daytime Sleepiness ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sleep Efficiency ◽  
Genome Wide Association Studies ◽  
Night Sleep ◽  
Inverse Variance ◽  
Point Increase ◽  
Increased Risk

Abstract Background Observational studies have indicated that there is a high prevalence of daytime sleepiness and night sleep changes in amyotrophic lateral sclerosis (ALS). However, the actual relation between these symptoms and ALS remains unclear. We aimed to determine whether daytime sleepiness and night sleep changes have an effect on ALS. Methods We used 2-sample mendelian randomization to estimate the effects of daytime sleepiness, sleep efficiency, number of sleep episodes and sleep duration on ALS. Summary statistics we used was from resent and large genome-wide association studies on the traits we chosen (n = 85,670–452,071) and ALS (cases n = 20,806, controls n = 59,804). Inverse variance weighted method was used as the main method for assessing causality. Results A genetically predicted 1-point increase in the assessment of daytime sleepiness was significantly associated with an increased risk of ALS (inverse-variance-weighted (IVW) odds ratio = 2.70, 95% confidence interval (CI): 1.27–5.76; P = 0.010). ALS was not associated with a genetically predicted 1-SD increase in sleep efficiency (IVW 1.01, 0.64–1.58; P = 0.973), Number of sleep episodes (IVW 1.02, 0.80–1.30; P = 0.859) or sleep duration (IVW 1.00, 1.00–1.01; P = 0.250). Conclusions Our results provide novel evidence that daytime sleepiness causes an increase in the risk of ALS and indicate that daytime sleepiness may be inherent in preclinical and clinical ALS patients, rather than simply affected by potential influencing factors.

Abstract P147: Genome Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases Using the UK Biobank Data

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yanjun Guo ◽  
Wonil Chung ◽  
Zhilei Shan ◽  
Liming Liang
Keyword(s):  
Cardiovascular Diseases ◽  
Genetic Correlation ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Cardiovascular Traits ◽  
Shared Genetic

Background: Patients with RA have a 2-10 folds increased risk of cardiovascular diseases (CVD) and CVD accounts for almost 50% of the excess mortality in patients with RA when compared with general population, but the mechanisms underlying such associations are largely unknown. Methods: We examined the genetic correlation, causality, and shared genetic variants between RA (Ncase=6,756, Ncontrol=452,476) and CVD (Ncase=44,246, Ncontrol=414,986) using LD Score regression (LDSC), generalized summary-data-based Mendelian Randomization (GSMR), and cross-trait meta-analysis in the UK Biobank Data. Results: In the present study, RA was significantly genetically correlated with MI, angina, CHD, and CVD after correcting for multiple testing (Rg ranges from 0.40 to 0.43, P<0.05/5). Interestingly, when stratified by frequent usage of aspirin and paracetamol, we observed increased genetic correlation between RA and CVD for participants without aspirin usage ( Rg increased to 0.54 [95%CI: 0.54, 0.78] for angina; P value=6.69х10 -6 ), and for participants with usage of paracetamol ( Rg increased to 0.75 [95%CI: 0.20, 1.29] for MI; P value=8.90х10 -3 ). Cross-trait meta-analysis identified 9 independent loci that were shared between RA and at least one of the genetically correlated CVD traits including PTPN22 at chr1p13.2 , BCL2L11 at chr2q13 , and CCR3 at chr3p21.31 ( P single trait <1х10 -3 and P meta <5х10 -8 ) highlighting potential shared etiology between them which include accelerating atherosclerosis and upregulating oxidative stress and vascular permeability. Finally, Mendelian randomization analyses observed inconsistent instrumental effects and were unable to conclude the causality and directionality between RA and CVD. Conclusion: Our results supported positive genetic correlation between RA and multiple cardiovascular traits, and frequent usage of aspirin and paracetamol may modify their associations, but instrumental analyses were unable to conclude the causality and directionality between them.

Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study

2020 ◽  
Vol 105 (12) ◽  
pp. e4688-e4698
Author(s):  
Zhi Cao ◽  
Chenjie Xu ◽  
Hongxi Yang ◽  
Shu Li ◽  
Fusheng Xu ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Cohort Study ◽  
Lower Risk ◽  
Serum Urate ◽  
Healthy Weight ◽  
Uk Biobank ◽  
Health Records ◽  
Increased Risk ◽  
The Uk

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

scholarly journals Mendelian randomization analysis of the association between human blood cell traits and uterine polyps

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuliu Sun ◽  
Yan Liu ◽  
Lanlan Li ◽  
Minjie Jiao ◽  
Yufen Jiang ◽  
...  
Keyword(s):  
Human Blood ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Random Effect ◽  
Sensitivity Analyses ◽  
Endometrial Polyps ◽  
Inverse Variance ◽  
Weighted Median ◽  
The Uk ◽  
Uterine Polyps

AbstractHuman blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79–0.93, P = 1.06 × 10−4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77–0.91, P = 2.43 × 10−5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

scholarly journals Irritable Bowel Syndrome and Migraine: Evidence From Mendelian Randomization Analysis in the UK Biobank

2021 ◽  
Author(s):  
Jie Chen ◽  
Xuejie Chen ◽  
Ying Xie ◽  
Yuhao Sun ◽  
Xiaoyan Wang ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Mendelian Randomization ◽  
Causal Association ◽  
Uk Biobank ◽  
Mendelian Randomization Analysis ◽  
Inverse Variance ◽  
Irritable Bowel ◽  
The Uk ◽  
And Control ◽  
Randomization Analysis

Abstract Background: IBS and Migraine are two diseases featuring high prevalence. Previous studies have suggested a relationship between Irritable Bowel Syndrome (IBS) and migraine, although the causal association remains unclear. We sought to explore the causal association between IBS and migraine, and to prove the importance of migraine prevention in IBS patients.Methods: This study used a two-sample Mendelian-randomization analysis to explore the association of IBS with migraine. Genetic association with migraine were acquired from the UK Biobank (UKB) genetic databases (cases: 1,072; controls: 360,122). We performed estimation using Inverse Variance Weighting (IVW), along with Maximum Likelihood, MR-RAPS, MR-Egger and Weighted Median for sensitivity analysis. Considering possible bias, we also conducted polymorphism, heterogeneity, and directional analysis.Results: The IVW estimation genetically predicted the causal association between IBS and migraine (OR=1.09, 95%CI 1.01 to 1.17, p=0.03). Neither statistical horizontal pleiotropy (MR Egger p=0.42; MR-PRESSO p=0.78) nor possible heterogeneity (IVW Q = 26.15, p=0.80) was found. Reverse causation was also not detected (p steiger<0.01).Conclusion: Mendelian randomization analysis supported a positive-going causal association of IBS with migraine, providing enlightenment for disease prevention and control.

scholarly journals Association of genetically predicted serum estradiol with risk of thromboembolism in men: A mendelian randomization study

2021 ◽  
Author(s):  
Maria Nethander ◽  
Johan Quester ◽  
Liesbeth Vandenput ◽  
Claes Ohlsson
Keyword(s):  
Ischemic Stroke ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Gene Region ◽  
Uk Biobank ◽  
Increased Risk ◽  
Self Reports ◽  
The Uk

Abstract Context An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men but a possible causal role of estradiol for risk of thromboembolism in men remains unknown. Objective To determine whether endogenous estradiol has a causal role in thromboembolism in men. Design Two-sample mendelian randomization study using gene-based genetic instruments Setting UK Biobank Participants We assessed the association between endogenous estradiol genetically predicted by 22 variants in the CYP19A1 gene region and risk of thromboembolism (5815 cases) in 170,593 unrelated men of white ancestry in the UK Biobank. Main Outcome Measure Thromboembolism based on self-reports, hospital episodes, and death. Results Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of thromboembolism (odds ratio per SD increase in estradiol 0.74, 95% confidence interval 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of ischemic stroke (0.68, 0.49-0.95) but not myocardial infarction (0.97, 0.84-1.13). Conclusions Genetically predicted estradiol was inversely associated with risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by aromatase (CYP19A1) activity, may contribute to the overall impact of sex steroids on thromboembolism in men.

scholarly journals Impact of Genetically Predicted Red Blood Cell Traits on Venous Thromboembolism: Multivariable Mendelian Randomization Study Using UK Biobank

2020 ◽  
Vol 9 (14) ◽  
Author(s):  
Shan Luo ◽  
Shiu Lun Au Yeung ◽  
Verena Zuber ◽  
Stephen Burgess ◽  
Catherine Mary Schooling
Keyword(s):  
Venous Thromboembolism ◽  
General Population ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
European Ancestry ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk

Background Red blood cell (RBC) transfusion and erythropoiesis‐stimulating agent administration are cornerstones of clinical practice, yet concerns exist as to potential increased risk of thrombotic events. This study aims to identify RBC traits most relevant to venous thromboembolism (VTE) and assess their genetically predicted effects on VTE in the general population. Methods and Results We used multivariable mendelian randomization with bayesian model averaging for exposure selection. We obtained genetic variants predicting any of 12 RBC traits from the largest genome‐wide association study of hematological traits (173 480 participants of European ancestry) and applied them to the UK Biobank (265 424 white British participants). We used univariable mendelian randomization methods as sensitivity analyses for validation. Among 265 424 unrelated participants in the UK Biobank, there were 9752 cases of VTE (4490 men and 5262 women). Hemoglobin was selected as the plausible important RBC trait for VTE (marginal inclusion probability=0.91). The best‐fitting model across all RBC traits contained hemoglobin only (posterior probability=0.46). Using the inverse variance–weighted method, genetically predicted hemoglobin was positively associated (odds ratio, 1.21 per g/dL unit of hemoglobin; 95% CI, 1.05–1.41) with VTE. Sensitivity analyses (mendelian randomization–Egger, weighted median, and mendelian randomization pleiotropy residual sum and outlier test) gave consistent estimates. Conclusions Endogenous hemoglobin is the key RBC trait causing VTE, with a detrimental effect in the general population on VTE. Given men have higher hemoglobin than women, this finding may help explain the sexual disparity in VTE rates. The benefits of therapies and other factors that raise hemoglobin need to be weighed against their risks.

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