scholarly journals Alcohol Consumption Is Associated with Poor Prognosis in Obese Patients with COVID-19: A Mendelian Randomization Study Using UK Biobank

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1592
Author(s):  
Xiude Fan ◽  
Zhengwen Liu ◽  
Kyle L. Poulsen ◽  
Xiaoqin Wu ◽  
Tatsunori Miyata ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Large Population ◽  
Heavy Drinking ◽  
Adaptive Immune Response ◽  
Population Based ◽  
Uk Biobank ◽  
Chronic Alcohol Abuse ◽  
Risk Of Death ◽  
Using Data

Background: Acute and chronic alcohol abuse has adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19. Methods: We conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50–83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated allele scores using three genetic variants (rs1229984 (Alcohol Dehydrogenase 1B, ADH1B), rs1260326 (Glucokinase Regulator, GCKR), and rs13107325 (Solute Carrier Family 39 Member 8, SLC39A8)) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participants with and without obesity. Results: Of the 12,937 participants, 4496 were never or infrequent drinkers and 8441 were frequent drinkers. Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with or without obesity (All q > 0.10). However, frequent drinking, especially heavy drinking (HR = 2.07, 95%CI 1.24–3.47; q = 0.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (All q < 0.10). Conclusions: Our findings suggest that alcohol consumption has adverse effects on the progression of COVID-19 in white participants with obesity, but was not associated with susceptibility to SARS-CoV-2 infection.

scholarly journals Alcohol Consumption is Associated with Poor Prognosis in Obese Patients with COVID-19: a Mendelian Randomization Study using UK Biobank

2020 ◽  
Author(s):  
Xiude Fan ◽  
Zhengwen Liu ◽  
Kyle L Poulsen ◽  
Xiaoqin Wu ◽  
Tatsunori Miyata ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Large Population ◽  
Heavy Drinking ◽  
Adaptive Immune Response ◽  
Population Based ◽  
Uk Biobank ◽  
Chronic Alcohol Abuse ◽  
Risk Of Death ◽  
Using Data

AbstractBackgroundAcute and chronic alcohol abuse have adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19.MethodWe conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50-83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated weighted and unweighted allele scores using three genetic variants (rs1229984, rs1260326, and rs13107325) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participates with and without obesity.ResultsOf the 12,937 participants, 4,496 were never or infrequent drinkers and 8,441 were frequent drinkers. (including 1,156 light drinkers, 3,795 moderate drinkers, and 3,490 heavy drinkers). Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with (OR=0.963, 95%CI 0.800-1.159; q =1.000) or without obesity (OR=0.891, 95%CI 0.755-1.053; q =.319). However, frequent drinking (HR=1.565, 95%CI 1.012-2.419; q =.079), especially heavy drinking (HR=2.071, 95%CI 1.235-3.472; q =.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (HR=1.480, 95%CI 1.059-2.069; q =.099).ConclusionsOur findings suggested alcohol consumption may had adverse effects on the progression of COVID-19 in white participants with obesity, but was not associate with susceptibility to SARS-CoV-2 infection.

scholarly journals Within-family studies for Mendelian randomization: avoiding dynastic, assortative mating, and population stratification biases

2019 ◽  
Author(s):  
Ben Brumpton ◽  
Eleanor Sanderson ◽  
Fernando Pires Hartwig ◽  
Sean Harrison ◽  
Gunnhild Åberge Vie ◽  
...  
Keyword(s):  
Population Stratification ◽  
Mendelian Randomization ◽  
Genetic Data ◽  
Population Based ◽  
Health Study ◽  
Uk Biobank ◽  
Family Effects ◽  
Family Based ◽  
Using Data ◽  
The Uk

AbstractMendelian randomization (MR) is a widely-used method for causal inference using genetic data. Mendelian randomization studies of unrelated individuals may be susceptible to bias from family structure, for example, through dynastic effects which occur when parental genotypes directly affect offspring phenotypes. Here we describe methods for within-family Mendelian randomization and through simulations show that family-based methods can overcome bias due to dynastic effects. We illustrate these issues empirically using data from 61,008 siblings from the UK Biobank and Nord-Trøndelag Health Study. Both within-family and population-based Mendelian randomization analyses reproduced established effects of lower BMI reducing risk of diabetes and high blood pressure. However, while MR estimates from population-based samples of unrelated individuals suggested that taller height and lower BMI increase educational attainment, these effects largely disappeared in within-family MR analyses. We found differences between population-based and within-family based estimates, indicating the importance of controlling for family effects and population structure in Mendelian randomization studies.

scholarly journals Gallstone disease, diabetes, calcium, triglycerides, smoking and alcohol consumption and pancreatitis risk: Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yuan ◽  
Edward L. Giovannucci ◽  
Susanna C. Larsson
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Pancreatitis ◽  
Alcohol Consumption ◽  
Mendelian Randomization ◽  
Gallstone Disease ◽  
Smoking Initiation ◽  
Disease Type ◽  
Uk Biobank ◽  
Increased Risk

AbstractWe conducted a Mendelian randomization study to determine the potential causal associations of gallstone disease, diabetes, serum calcium, triglyceride levels, smoking and alcohol consumption with acute and chronic pancreatitis. Genetic variants associated with the exposures at p < 5 × 10−8 were selected from corresponding genome-wide association studies. Summary-level data for pancreatitis were obtained from the FinnGen consortium and UK Biobank. Univariable and multivariable Mendelian randomization analyses were performed and results from FinnGen and UK Biobank were combined using the fixed-effects meta-analysis method. Genetic predisposition to gallstone disease, type 2 diabetes and smoking initiation was associated with an increased risk of acute pancreatitis. The combined odds ratios (ORs) were 1.74 (95% confidence interval (CI), 1.57, 1.93) for gallstone disease, 1.14 (95% CI, 1.06, 1.21) for type 2 diabetes and 1.56 (95% CI, 1.32, 1.83) for smoking initiation. The association for type 2 diabetes attenuated after adjustment for gallstone disease. Genetic predisposition to gallstone disease and smoking initiation as well as higher genetically predicted serum calcium and triglyceride levels were associated with an increased risk of chronic pancreatitis. The combined ORs of chronic pancreatitis were 1.27 (95% CI, 1.08, 1.50) for gallstone disease, 1.86 (95% CI, 1.43, 2.43) for smoking initiation, 2.20 (95% CI, 1.30, 3.72) for calcium and 1.47 (95% CI, 1.23, 1.76) for triglycerides. This study provides evidence in support that gallstone disease, type 2 diabetes, smoking and elevated calcium and triglyceride levels are causally associated with the risk of acute or chronic pancreatitis.

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

Platelet Indices and Risk of Death and Cardiovascular Events: Results from a Large Population-Based Cohort Study

2019 ◽  
Vol 119 (11) ◽  
pp. 1773-1784 ◽  
Author(s):  
Giuseppe Patti ◽  
Giuseppe Di Martino ◽  
Fabrizio Ricci ◽  
Giulia Renda ◽  
Sabina Gallina ◽  
...  
Keyword(s):  
Platelet Count ◽  
Ischemic Stroke ◽  
Adverse Events ◽  
Large Population ◽  
Previous History ◽  
Population Based ◽  
Platelet Indices ◽  
Risk Of Death ◽  
Previous Stroke ◽  
History Of

AbstractStudies evaluating the relationship between platelet indices and cardiovascular (CV) outcomes yielded conflicting results. We assessed the incidence of adverse events according to baseline quintiles of platelet indices in the prospective cohort of the Malmö Diet and Cancer Study. A total of 30,314 individuals (age 57 ± 8 years) were followed for a median of 16 years (468,490 person-years). Outcome measures included all-cause death, CV death, myocardial infarction (MI), and ischemic stroke. The fifth quintile of platelet count (> 274.6 × 109/L) was associated with higher incidence of all-cause death (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09–1.32, p < 0.001), CV death (HR 1.19, 95% CI 1.00–1.42; p = 0.044), MI (HR 1.32, 95% CI 1.12–1.54; p = 0.001), and ischemic stroke (HR 1.27, 95% CI 1.08–1.50, p = 0.004) compared with the first quintile (≤ 185 × 109/L), and also associated with a lower survival, regardless of previous history of MI (p for interaction = 0.58) or stroke (p for interaction = 0.42). In the highest quintile, history of stroke had a higher risk of CV death (HR 3.18, 95% CI 1.54–6.54) compared with no previous stroke (HR 1.12, 95% CI 0.96–1.31). The risk of MI and stroke was greatest in the fifth quintile, regardless of previous MI or previous stroke, respectively. The risk of all adverse events was similar across different quintiles of mean platelet volume. In conclusion, elevated platelet count is associated with higher mortality and risk of CV events, regardless of previous MI and stroke. Platelet count may thus be a useful marker for further stratification of CV risk, and especially of death.

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

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.

scholarly journals Factorial Mendelian randomization: using genetic variants to assess interactions

2019 ◽  
Vol 49 (4) ◽  
pp. 1147-1158 ◽  
Author(s):  
Jessica M B Rees ◽  
Christopher N Foley ◽  
Stephen Burgess
Keyword(s):  
Risk Factors ◽  
Instrumental Variables ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Real Data ◽  
Uk Biobank ◽  
Pharmacological Interventions ◽  
Natural Break ◽  
Using Data ◽  
Randomization Analysis

Abstract Background Factorial Mendelian randomization is the use of genetic variants to answer questions about interactions. Although the approach has been used in applied investigations, little methodological advice is available on how to design or perform a factorial Mendelian randomization analysis. Previous analyses have employed a 2 × 2 approach, using dichotomized genetic scores to divide the population into four subgroups as in a factorial randomized trial. Methods We describe two distinct contexts for factorial Mendelian randomization: investigating interactions between risk factors, and investigating interactions between pharmacological interventions on risk factors. We propose two-stage least squares methods using all available genetic variants and their interactions as instrumental variables, and using continuous genetic scores as instrumental variables rather than dichotomized scores. We illustrate our methods using data from UK Biobank to investigate the interaction between body mass index and alcohol consumption on systolic blood pressure. Results Simulated and real data show that efficiency is maximized using the full set of interactions between genetic variants as instruments. In the applied example, between 4- and 10-fold improvement in efficiency is demonstrated over the 2 × 2 approach. Analyses using continuous genetic scores are more efficient than those using dichotomized scores. Efficiency is improved by finding genetic variants that divide the population at a natural break in the distribution of the risk factor, or else divide the population into more equal-sized groups. Conclusions Previous factorial Mendelian randomization analyses may have been underpowered. Efficiency can be improved by using all genetic variants and their interactions as instrumental variables, rather than the 2 × 2 approach.

scholarly journals Generalised anxiety disorder and hospital admissions: findings from a large, population cohort study

BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e018539 ◽  
Author(s):  
Olivia Remes ◽  
Nicholas Wainwright ◽  
Paul Surtees ◽  
Louise Lafortune ◽  
Kay-Tee Khaw ◽  
...  
Keyword(s):  
Anxiety Disorder ◽  
Service Use ◽  
Hospital Admissions ◽  
Late Onset ◽  
Large Population ◽  
Population Based ◽  
Generalised Anxiety Disorder ◽  
Increased Risk ◽  
Using Data ◽  
Administrative Health Databases

ObjectiveGeneralised anxiety disorder (GAD) is the most common anxiety disorder in the general population and has been associated with high economic and human burden. However, it has been neglected in the health services literature. The objective of this study is to assess whether GAD leads to hospital admissions using data from the European Prospective Investigation of Cancer-Norfolk. Other aims include determining whether early-onset or late-onset forms of the disorder, episode chronicity and frequency, and comorbidity with major depressive disorder (MDD) contribute to hospital admissions.DesignLarge, population study.SettingUK population-based cohort.Participants30 445 British participants were recruited through general practice registers in England. Of these, 20 919 completed a structured psychosocial questionnaire used to identify presence of GAD. Anxiety was assessed in 1996–2000, and health service use was captured between 1999/2000 and 2009 through record linkage with large, administrative health databases. 17 939 participants had complete data on covariates.Main outcome measurePast-year GAD defined according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition.ResultsIn this study, there were 2.2% (393/17 939) of respondents with GAD. Anxiety was not independently associated with hospital admissions (incidence rate ratio (IRR)=1.04, 95% CI 0.90 to 1.20) over 9 years. However, those whose anxiety was comorbid with depression showed a statistically significantly increased risk for hospital admissions (IRR=1.23, 95% CI 1.02 to 1.49).ConclusionPeople with GAD and MDD comorbidity were at an increased risk for hospital admissions. Clinicians should consider that meeting criteria for a pure or individual disorder at one point in time, such as past-year GAD, does not necessarily predict deleterious health outcomes; rather different forms of the disorder, such as comorbid cases, might be of greater importance.

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