scholarly journals A combination of variant genotypes at two loci in the APOL1 gene is associated with adverse outcomes in SARS-CoV-2: a UK Biobank study.

2021 ◽  
Author(s):  
Walt E Adamson ◽  
Harry Noyes ◽  
Georgia Beckett-Hill ◽  
Anneli Cooper ◽  
Annette MacLeod
Keyword(s):  
African Ancestry ◽  
Central Africa ◽  
Population Level ◽  
Adverse Outcomes ◽  
Contributory Factor ◽  
Uk Biobank ◽  
Geographical Regions ◽  
Using Data ◽  
The Individual ◽  
The Uk

The risk of hospitalisation or death from Covid-19 in the UK is disproportionately higher in black ethnic populations than others for reasons that are not fully understood (1). In people of African ancestry, variants of the APOL1 gene (G1 and G2) have been associated with risk of a number of non-communicable diseases, such as chronic kidney disease (2,3,4,5) and the infectious disease, African sleeping sickness (6). Here we test the hypothesis that adverse Covid-19 outcomes are also associated with these variants. Using data from Black UK Biobank participants, we used Firth's Bias-Reduced Logistic Regression in R to identify APOL1 genotypes that were associated with either hospitalisation or death. APOL1 G1/G2 compound heterozygotes were associated with hospitalisation (OR = 2.4 95% CI: 1.2-4.5) p = 0.010) and death (OR = 5.4, 95% CI: 1.8-15.4, p = 0.004) compared to individuals not carrying the variants. This support hypotheses proposing APOL1 genotype (specifically G1/G2) is a significant contributory factor in the increased rates of poor Covid-19 outcomes observed in people of African ancestry. This has implications for both at the individual and population level by identifying those at higher risk of severe Covid-19 who would benefit from early vaccination and treatment. This is especially relevant to geographical regions where APOL1 G1/G2 genotypes are common such as West and Central Africa (6) and their diaspora.

scholarly journals A socially patterned Biological Health Score and mortality in Understanding Society and UKBiobank

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
M Chadeau-Hyam ◽  
M Karimi ◽  
R Castagné ◽  
B Bodinier ◽  
C Delpierre ◽  
...  
Keyword(s):  
Uk Biobank ◽  
Health Score ◽  
Specific Mortality ◽  
Wear And Tear ◽  
Disease Specific Mortality ◽  
Biological Health ◽  
Using Data ◽  
The Uk ◽  
Disease Specific ◽  
Physiological Systems

Abstract Background It now established that social factors impact the quality of ageing, through the lifecourse stimulation/dysregulation of key physiological systems. Composite scores such as allostatic load, focusing on the response to stress, can be used to measure individual physiological wear-and-tear. Methods Using data from the Understanding Society study, a cross-sectional panel study including 9,088 participants representative of the UK population, we defined a synthetic biological health score (BHS) capturing the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular, and metabolic systems), and of two key organs (liver and kidney). We used 16 established blood-derived biomarkers of these systems to calculate the BHS and explored the relative contribution of socio-economic position to the BHS and its main components across age groups. Using data from UK biobank, including over 400,000 UK participants in whom similar biomarkers have been assayed in blood, we sought validation of our results and investigated the role of the BHS on all-cause and disease specific mortality, and disease incidence. Results We identified a systematic decreasing education-related gradient of the BHS (p < 0·001) leading to lower biological risk in participants with higher educational attainment. Education-related differences in the BHS were detected early in life, and were not attributable to lifestyle and behavioural factors. Analyses of the UK biobank data validated these findings and also showed that the BHS contributed in turn, irrespective of established health risk factors, to all-cause and disease specific mortality. Interpretation Our findings highlight the social-to-biological processes ultimately leading to health inequalities, and suggest that such disparities can already be detected in the 20-40 year age group.

scholarly journals Phenotypic and genetic characterization of lower LDL-C and increased type-2 diabetes risk in the UK Biobank

2020 ◽  
Author(s):  
Ada Admin ◽  
Yann C. Klimentidis ◽  
Amit Arora ◽  
Michelle Newell ◽  
Jin Zhou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Uk Biobank ◽  
Alcoholic Fatty Liver ◽  
Genome Wide ◽  
Using Data ◽  
Underlying Mechanisms ◽  
Phenotypic And Genetic Characterization ◽  
The Uk

Although hyperlipidemia is traditionally considered a risk factor for type-2 diabetes (T2D), evidence has emerged from statin trials and candidate gene investigations suggesting that lower LDL-C increases T2D risk. We thus sought to more comprehensively examine the phenotypic and genotypic relationships of LDL-C with T2D. Using data from the UK Biobank, we found that levels of circulating LDL-C were negatively associated with T2D prevalence (OR=0.41[0.39, 0.43] per mmol/L unit of LDL-C), despite positive associations of circulating LDL-C with HbA1c and BMI. We then performed the first genome-wide exploration of variants simultaneously associated with lower circulating LDL-C and increased T2D risk, using data on LDL-C from the UK Biobank (n=431,167) and the GLGC consortium (n=188,577), and T2D from the DIAGRAM consortium (n=898,130). We identified 31 loci associated with lower circulating LDL-C and increased T2D, capturing several potential mechanisms. Seven of these loci have previously been identified for this dual phenotype, and 9 have previously been implicated in non-alcoholic fatty liver disease. These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C, and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C-lowering medications.

scholarly journals Phenome-wide burden of copy number variation in UK Biobank

2019 ◽  
Author(s):  
Matthew Aguirre ◽  
Manuel Rivas ◽  
James Priest
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Significant Proportion ◽  
High Body Mass Index ◽  
Population Level ◽  
Copy Number Variations ◽  
Uk Biobank ◽  
Number Variation ◽  
Artery Disease ◽  
The Uk

AbstractCopy number variations (CNV) represent a significant proportion of the genetic differences between individuals and many CNVs associate causally with syndromic disease and clinical outcomes. Here, we characterize the landscape of copy number variation and their phenome-wide effects in a sample of 472,228 array-genotyped individuals from the UK Biobank. In addition to population-level selection effects against genic loci conferring high-mortality, we describe genetic burden from syndromic and previously uncharacterized CNV loci across nearly 2,000 quantitative and dichotomous traits, with separate analyses for common and rare classes of variation. Specifically, we highlight the effects of CNVs at two well-known syndromic loci 16p11.2 and 22q11.2, as well as novel associations at 9p23, in the context of acute coronary artery disease and high body mass index. Our data constitute a deeply contextualized portrait of population-wide burden of copy number variation, as well as a series of known and novel dosage-mediated genic associations across the medical phenome.

scholarly journals Vaccination and Non-Pharmaceutical Interventions: When can the UK relax about COVID-19?

2021 ◽  
Author(s):  
Sam Moore ◽  
Edward M. Hill ◽  
Michael J. Tildesley ◽  
Louise Dyson ◽  
Matt J. Keeling
Keyword(s):  
Perceived Risk ◽  
Immunisation Programme ◽  
Population Level ◽  
Epidemiological Data ◽  
Vaccine Uptake ◽  
Severe Illness ◽  
Individual Level ◽  
The Individual ◽  
The Uk ◽  
Pharmaceutical Interventions

AbstractThe announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines. In this study we use an age-structured mathematical model, matched to a range of epidemiological data, to consider the interaction between the UK vaccination programme and future relaxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infections, and the individual-level risk relative to vaccine status. While the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the transmission blocking action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries.

scholarly journals Modelling the distribution of white matter hyperintensities due to ageing on MRI images using Bayesian inference

2018 ◽  
Author(s):  
Vaanathi Sundaresan ◽  
Ludovica Griffanti ◽  
Petya Kindalova ◽  
Fidel Alfaro-Almagro ◽  
Giovanna Zamboni ◽  
...  
Keyword(s):  
White Matter ◽  
Vascular Disease ◽  
White Matter Hyperintensities ◽  
Age Groups ◽  
Clinical Importance ◽  
Population Level ◽  
Distribution Model ◽  
Ageing Population ◽  
Uk Biobank ◽  
The Uk

AbstractWhite matter hyperintensities (WMH), also known as white matter lesions, are localised white matter areas that appear hyperintense on MRI scans. WMH commonly occur in the ageing population, and are often associated with several factors such as cognitive disorders, cardiovascular risk factors, cerebrovascular and neurodegenerative diseases. Despite the fact that some links between lesion location and parametric factors such as age have already been established, the relationship between voxel-wise spatial distribution of lesions and these factors is not yet well understood. Hence, it would be of clinical importance to model the distribution of lesions at the population-level and quantitatively analyse the effect of various factors on the lesion distribution model.In this work we compare various methods, including our proposed method, to generate voxel-wise distributions of WMH within a population with respect to various factors. Our proposed Bayesian spline method models the spatio-temporal distribution of WMH with respect to a parametric factor of interest, in this case age, within a population. Our probabilistic model takes as input the lesion segmentation binary maps of subjects belonging to various age groups and provides a population-level parametric lesion probability map as output. We used a spline representation to ensure a degree of smoothness in space and the dimension associated with the parameter, and formulated our model using a Bayesian framework.We tested our algorithm output on simulated data and compared our results with those obtained using various existing methods with different levels of algorithmic and computational complexity. We then compared the better performing methods on a real dataset, consisting of 1000 subjects of the UK Biobank, divided in two groups based on hypertension diagnosis. Finally, we applied our method on a clinical dataset of patients with vascular disease.On simulated dataset, the results from our algorithm showed a mean square error (MSE) value of 7.27 × 10−5, which was lower than the MSE value reported in the literature, with the advantage of being robust and computationally efficient. In the UK Biobank data, we found that the lesion probabilities are higher for the hypertension group compared to the non-hypertension group and further verified this finding using a statistical t-test. Finally, when applying our method on patients with vascular disease, we observed that the overall probability of lesions is significantly higher in later age groups, which is in line with the current literature.

scholarly journals O3B.5 The mental health of police, firefighters and paramedics in the UK biobank: a comparison with the general working population

2019 ◽  
Vol 76 (Suppl 1) ◽  
pp. A24.3-A25
Author(s):  
Sharon Stevelink ◽  
Nicola Fear ◽  
Matthew Hotopf
Keyword(s):  
Mental Health ◽  
Random Sample ◽  
Emergency Services ◽  
Life Time ◽  
Uk Biobank ◽  
Post Traumatic Stress ◽  
Emergency Services Personnel ◽  
Working People ◽  
Using Data ◽  
The Uk

It is our responsibility to protect and look after the health of members of the emergency services as this directly impacts on the country’s readiness to respond to these disasters and is a critical part of our duty of care towards this important group of workers. This study examined the mental health outcomes and associations with individual and job characteristics among emergency services personnel compared to a random sample of working people, thereby using data from the UK Biobank. This data source contains data on over half a million adults in the UK, who were at the time of recruitment between 40–69 years. Over 2 80 000 reported being in work. Current emergency services personnel were identified based on Standard Occupational Classification (SOC) 2000 codes. A random sample of age and sex matched people working in other occupations were selected from the UK Biobank for comparative purposes. The prevalence of the outcomes of interest, based on current and life time measures of depression, anxiety, alcohol misuse, post-traumatic stress disorder, suicide and trauma will be presented. The findings will be discussed in the light of current policies and strategies and recommendations for further practice will be outlined.

MO023SARCOPENIA, CHRONIC KIDNEY DISEASE AND RISK OF MORTALITY: FINDINGS FROM 426,839 INDIVIDUALS IN THE UK BIOBANK

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Thomas Wilkinson ◽  
Joanne Miksza ◽  
Luke Baker ◽  
Courtney Lightfoot ◽  
Emma Watson ◽  
...  
Keyword(s):  
Muscle Mass ◽  
Early Stage ◽  
Handgrip Strength ◽  
Functional Decline ◽  
Adverse Outcomes ◽  
Survival Models ◽  
Uk Biobank ◽  
All Cause Mortality ◽  
Comparative Group ◽  
The Uk

Abstract Background and Aims Sarcopenia describes a degenerative and generalised skeletal muscle disorder involving the loss of muscle mass and function. In studies of the general population, sarcopenia is associated with adverse outcomes including falls, functional decline, frailty, and mortality. However it remains an under-recognised yet important clinical problem in an ever-increasing ageing and multimorbid renal population. Whilst sarcopenia has been widely studied in end-stage renal disease, there is limited evidence of its prevalence and effects in those not requiring dialysis, particularly in large cohort studies and using the latest sarcopenia definitions. Using the UK Biobank, we aimed to identify the prevalence of sarcopenia in individuals with non-dialysis CKD and its association with mortality. Method 426,839 participants were categorised into a CKD (defined as eGFR <60ml/min/1.73m2 not requiring dialysis) and a non-CKD comparative group (no evidence of CKD). Sarcopenia was diagnosed using criteria from the EWGSOP2: ‘probable sarcopenia’ (low handgrip strength (HGS) <27 and 16kg, males and females respectively); ‘confirmed sarcopenia’ (low HGS plus low muscle mass, appendicular lean mass <7.0 and 5.5 kg/m2 as measured by bioelectrical impedance); and ‘severe sarcopenia’ (low HGS and muscle mass plus slow gait speed). Patients requiring existing renal replacement therapy were excluded. All-cause mortality was extracted from data linkage to national death records with a median follow up of 9.0 years. Data were analysed using Cox survival models. Results CKD (non-dialysis dependent) was identified in n=7,623 individuals (mean age 62.7 (±5.9) years, 44% male, eGFR 52.5 (±7.7) ml/min/1.73m2) compared to n=419,216 in the non-CKD comparative group (mean age 56.1 (±8.1) years, 47% male). ‘Probable sarcopenia’ was identified in 9% of individuals with CKD compared to 5% in those without CKD (P<0.001). ‘Confirmed sarcopenia’ was observed in 0.3% of those with CKD (vs. 0.2% in the non-CKD group, P<0.001). 0.2% of CKD patients satisfied all three criteria (‘severe sarcopenia’) compared to 0.03% in those without CKD (P<0.001). In CKD, sarcopenia was significantly associated with all-cause mortality: ‘probable sarcopenia’, unadjusted hazard ratio (HR) 1.95 (95%CI 1.57 to 2.42), P<0.001 (Figure 1); ‘confirmed sarcopenia’, HR 5.1 (2.5 to 10.3) P<0.001; ‘severe sarcopenia’, HR 5.1 (1.9 to 13.5) P=0.001. Conclusion In the largest cohort of its kind, probable sarcopenia was present in 9% of individuals with non-dialysis CKD. The risk of sarcopenia was significantly higher in those with CKD than those without. Regardless of criteria used, CKD patients with sarcopenia were approximately 2-5 times more likely to die than those without sarcopenia. Worryingly, the risk of sarcopenia was elevated even in patients with early stage mild to moderate CKD. Our results show that sarcopenia, including just the presence of low muscle strength, is an important predictor of mortality in early non-dialysis CKD. Measuring sarcopenia as standard practice may identify those most at risk of future adverse events and in need of appropriate interventions to mitigate its negative effects.

scholarly journals A data linkage study of suspected seizures in the urgent and emergency care system in the UK

2020 ◽  
Vol 37 (10) ◽  
pp. 605-610
Author(s):  
Thomas Hughes-Gooding ◽  
Jon M Dickson ◽  
Colin O'Keeffe ◽  
Suzanne M Mason
Keyword(s):  
Emergency Care ◽  
Data Linkage ◽  
Models Of Care ◽  
Linkage Study ◽  
Adverse Outcomes ◽  
Published Data ◽  
Full Potential ◽  
Cross Sectional ◽  
Using Data ◽  
The Uk

IntroductionThe urgent and emergency care (UEC) system is struggling with increased demand, some of which is clinically unnecessary. Patients suffering suspected seizures commonly present to EDs, but most seizures are self-limiting and have low risk of short-term adverse outcomes. We aimed to investigate the flow of suspected seizure patients through the UEC system using data linkage to facilitate the development of new models of care.MethodsWe used a two-stage process of deterministic linking to perform a cross-sectional analysis of data from adults in a large region in England (population 5.4 million) during 2014. The core dataset comprised a total of 739 436 ambulance emergency incidents, 1 033 778 ED attendances and 362 358 admissions.ResultsA high proportion of cases were successfully linked (86.9% ED-inpatient, 77.7% ED-ambulance). Suspected seizures represented 2.8% of all ambulance service incidents. 61.7% of these incidents led to dispatch of a rapid-response ambulance (8 min) and 72.1% were conveyed to hospital. 37 patients died before being conveyed to hospital and 24 died in the ED (total 61; 0.3%). The inpatient death rate was 0.4%. Suspected seizures represented 0.71% of ED attendances, 89.8% of these arrived by emergency ambulance, 45.4% were admitted and 44.5% of these admissions lasted under 48 hours.ConclusionsThis study confirms previously published data from smaller unlinked datasets, validating the linkage method, and provides new data for suspected seizures. There are significant barriers to realising the full potential of data linkage. Collaborative action is needed to create facilitative governance frameworks and improve data quality and analytical capacity.

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