Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank

Background: UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement. Methods: During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results. Results: The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor. Conclusions: Rigorous approaches related to sample collection, processing, retrieval, assay measurement and data analysis have been taken to mitigate the impact of both systematic and random variation in epidemiological analyses that use the biochemistry assay data in UK Biobank.

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Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank

Wellcome Open Research ◽

10.12688/wellcomeopenres.16171.2 ◽

2021 ◽

Vol 5 ◽

pp. 222

Author(s):

Naomi E. Allen ◽

Matthew Arnold ◽

Sarah Parish ◽

Michael Hill ◽

Simon Sheard ◽

...

Keyword(s):

Uk Biobank ◽

Sample Collection ◽

Sodium Potassium ◽

Reactive Protein ◽

Serum Assay ◽

Wide Range ◽

Epidemiological Impact ◽

The Uk ◽

The Impact ◽

Random Variation

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Systematic single-variant and gene-based association testing of 3,700 phenotypes in 281,850 UK Biobank exomes

10.1101/2021.06.19.21259117 ◽

2021 ◽

Author(s):

Konrad Karczewski ◽

Matthew Solomonson ◽

Katherine R Chao ◽

Julia K Goodrich ◽

Grace Tiao ◽

...

Keyword(s):

Sequence Data ◽

Association Studies ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Genetic Associations ◽

Allelic Series ◽

Association Analyses ◽

Wide Range ◽

The Uk ◽

The Impact

Genome-wide association studies have successfully discovered thousands of common variants associated with human diseases and traits, but the landscape of rare variation in human disease has not been explored at scale. Exome sequencing studies of population biobanks provide an opportunity to systematically evaluate the impact of rare coding variation across a wide range of phenotypes to discover genes and allelic series relevant to human health and disease. Here, we present results from systematic association analyses of 3,700 phenotypes using single-variant and gene tests of 281,850 individuals in the UK Biobank with exome sequence data. We find that the discovery of genetic associations is tightly linked to frequency as well as correlated with metrics of deleteriousness and natural selection. We highlight biological findings elucidated by these data and release the dataset as a public resource alongside a browser framework for rapidly exploring rare variant association results.

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Cardiovascular-related deaths at the beginning of the COVID-19 outbreak: a prospective analysis based on the UK Biobank

BMJ Open ◽

10.1136/bmjopen-2020-046931 ◽

2021 ◽

Vol 11 (6) ◽

pp. e046931

Author(s):

Junren Wang ◽

Jianwei Zhu ◽

Huazhen Yang ◽

Yao Hu ◽

Yajing Sun ◽

...

Keyword(s):

Primary Diagnosis ◽

Secondary Outcome ◽

Hospital Inpatient ◽

Reference Period ◽

Stress Reactions ◽

Uk Biobank ◽

The Uk ◽

The Impact ◽

Distinct Increase ◽

Related Mortality

ObjectiveTo assess the impact of the COVID-19 outbreak on cardiovascular disease (CVD) related mortality and hospitalisation.DesignCommunity-based prospective cohort study.SettingThe UK Biobank.Participants421 372 UK Biobank participants who were registered in England and alive as of 1 January 2020.Primary and secondary outcome measuresThe primary outcome of interest was CVD-related death, which was defined as death with CVD as a cause in the death register. We retrieved information on hospitalisations with CVD as the primary diagnosis from the UK Biobank hospital inpatient data. The study period was 1 January 2020 to June 30 2020, and we used the same calendar period of the three preceding years as the reference period. In order to control for seasonal variations and ageing of the study population, standardised mortality/incidence ratios (SMRs/SIRs) with 95% CIs were used to estimate the relative risk of CVD outcomes during the study period, compared with the reference period.ResultsWe observed a distinct increase in CVD-related deaths in March and April 2020, compared with the corresponding months of the three preceding years. The observed number of CVD-related deaths (n=218) was almost double in April, compared with the expected number (n=120) (SMR=1.82, 95% CI 1.58 to 2.07). In addition, we observed a significant decline in CVD-related hospitalisations from March onwards, with the lowest SIR observed in April (0.45, 95% CI 0.41 to 0.49).ConclusionsThere was a distinct increase in the number of CVD-related deaths in the UK Biobank population at the beginning of the COVID-19 outbreak. The shortage of medical resources for hospital care and stress reactions to the pandemic might have partially contributed to the excess CVD-related mortality, underscoring the need of sufficient healthcare resources and improved instructions to the public about seeking healthcare in a timely way.

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Evaluating the efficacy of technical measures: a case study of selection device legislation in the UK Crangon crangon (brown shrimp) fishery

ICES Journal of Marine Science ◽

10.1093/icesjms/fsn016 ◽

2008 ◽

Vol 65 (2) ◽

pp. 267-275 ◽

Cited By ~ 18

Author(s):

Tom L. Catchpole ◽

Andrew S. Revill ◽

James Innes ◽

Sean Pascoe

Keyword(s):

Brown Shrimp ◽

Crangon Crangon ◽

Shrimp Fishery ◽

The North ◽

Ex Post ◽

Wide Range ◽

The Uk ◽

The Impact ◽

Technical Measures

Abstract Catchpole, T. L., Revill, A. S., Innes, J., and Pascoe, S. 2008. Evaluating the efficacy of technical measures: a case study of selection device legislation in the UK Crangon crangon (brown shrimp) fishery. – ICES Journal of Marine Science, 65: 267–275. Bycatch reduction devices are being introduced into a wide range of fisheries, with shrimp and prawn fisheries particularly targeted owing to the heavy discarding common in these fisheries. Although studies are often undertaken to estimate the impact of a technical measure on the fishery before implementation, rarely have the impacts been assessed ex post. Here, the efficacy of the UK legislation pertaining to the use of sievenets in the North Sea Crangon crangon fishery is assessed. Three impacts were evaluated: on fisher behaviour (social), on the level of bycatch (biological), and on vessel profitability (economic). An apparent high level of compliance by skippers was identified despite a low level of enforcement. The estimated reduction in fleet productivity following the introduction of the legislation was 14%, equalling the mean loss of Crangon landings when using sievenets calculated from catch comparison trawls. Sievenets did reduce the unnecessary capture of unwanted marine organisms, but were least effective at reducing 0-group plaice, which make up the largest component of the bycatch. Clearly the legislation has had an effect in the desired direction, but it does not address sufficiently the bycatch issue in the Crangon fishery.

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Diet and general cognitive ability in the UK Biobank dataset

Scientific Reports ◽

10.1038/s41598-021-91259-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Piril Hepsomali ◽

John A. Groeger

Keyword(s):

Cognitive Ability ◽

Dietary Patterns ◽

Red Meat ◽

Milk Intake ◽

Special Focus ◽

General Cognitive Ability ◽

Food Groups ◽

Uk Biobank ◽

Wide Range ◽

The Uk

AbstractAccumulating evidence suggests that dietary interventions might have potential to be used as a strategy to protect against age-related cognitive decline and neurodegeneration, as there are associations between some nutrients, food groups, dietary patterns, and some domains of cognition. In this study, we aimed to conduct the largest investigation of diet and cognition to date, through systematically examining the UK Biobank (UKB) data to find out whether dietary quality and food groups play a role on general cognitive ability. This cross-sectional population-based study involved 48,749 participants. UKB data on food frequency questionnaire and cognitive function were used. Also, healthy diet, partial fibre intake, and milk intake scores were calculated. Adjusted models included age, sex, and BMI. We observed associations between better general cognitive ability and higher intakes of fish, and unprocessed red meat; and moderate intakes of fibre, and milk. Surprisingly, we found that diet quality, vegetable intake, high and low fibre and milk intake were inversely associated with general cognitive ability. Our results suggest that fish and unprocessed red meat and/or nutrients that are found in fish and unprocessed red meat might be beneficial for general cognitive ability. However, results should be interpreted in caution as the same food groups may affect other domains of cognition or mental health differently. These discrepancies in the current state of evidence invites further research to examine domain-specific effects of dietary patterns/food groups on a wide range of cognitive and affective outcomes with a special focus on potential covariates that may have an impact on diet and cognition relationship.

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The EU as an “enforcement patchwork”: the impact of national enforcement for compliance with EU water law in Spain and Britain

Journal of Public Policy ◽

10.1017/s0143814x13000238 ◽

2013 ◽

Vol 34 (2) ◽

pp. 331-353 ◽

Cited By ~ 3

Author(s):

Mónica García Quesada

Keyword(s):

Waste Water Treatment ◽

National Level ◽

State Level ◽

Detailed Examination ◽

Deterrent Effect ◽

Eu Law ◽

Wide Range ◽

The Uk ◽

The Impact ◽

The Eu

AbstractFailures of compliance with European Union (EU) directives have revealed the EU as a political system capable of enacting laws in a wide range of different policy areas, but facing difficulties to ensure their actual implementation. Although the EU relies on national enforcement agencies to ensure compliance with the EU legislation, there is scarce analysis of the differential deterrent effect of national enforcement in EU law compliance. This article examines the enforcement of an EU water directive, the Urban Waste Water Treatment Directive, in Spain and the UK. It focuses on the existing national sanctions for disciplining actors in charge of complying with EU requirements, and on the actual use of punitive sanctions. The analysis shows that a more comprehensive and active disciplinary regime at the national level contributes to explain a higher degree of compliance with EU law. The article calls for a detailed examination of the national administrative and criminal sanction system for a more comprehensive understanding of the incentives and disincentives to comply with EU law at the national state level.

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COVID-VU an ENT UK National Survey of Flexible Nasendoscopy in the Upper Aerodigestive Tract Amidst the COVID-19 Pandemic

10.21203/rs.3.rs-673407/v1 ◽

2021 ◽

Author(s):

Avgi Loizidou ◽

Taranjit Singh Tatla ◽

Ian Harvey ◽

Miriayi Aibibula ◽

Justin Roe ◽

...

Keyword(s):

Aerodigestive Tract ◽

Upper Aerodigestive Tract ◽

Speech And Language ◽

National Guidelines ◽

Healthcare Settings ◽

Wide Range ◽

Window Opening ◽

Operating Theatres ◽

The Uk ◽

The Impact

Abstract BackgroundFlexible nasendoscopy (FNE) is an invaluable multi-disciplinary tool for upper aerodigestive tract (UADT) examination. During the COVID-19 pandemic concerns were raised that FNE had the potential of generating aerosols resulting in human cross-contamination when performed on SARS-COV2 carriers. In the UK, and other European countries, national guidelines were issued restricting FNE to essential cases. We surveyed ENT UK members and Royal College of Speech and Language Therapists (RCSLT) members to determine the impact of the COVID-19 pandemic (first peak) on FNE practice in the UK.MethodsAn observational internet-based survey constructed in accordance to the CHERRIES checklist and setup in SurveyMonkeyof FNE practice amongst UK-based ENT surgeons and speech and language therapists in community clinics, the outpatient department, inpatient wards, ICU, emergency department and operating theatres (through the NHS and private sector) prior to, during and following the first COVID-19 wave in the UK. Results 314 responses collected (24% response rate), 82% from ENT clinicians, 17% from SLTs and 1% from other allied healthcare professionals. Overall, there has been a large reduction in the volume and indications for FNE during the first peak of the COVID-19 pandemic with limited recovery by mid-August 2020. Cancer and airway assessments were impacted less. A wide range of FNE protocols influenced by local factors are reported, varying in endoscope preference, Personal Protective Equipment (PPE) and sterilization methods. Where dedicated Aerosol Generating Procedure (AGP) rooms were unavailable, clinicians resorted to window opening and variable room “down-time” between patients. Endoscope preference reflected availability and user familiarity, ENT trainees favoring the use of single-use video endoscopes. ConclusionDespite national guidance, local practice of FNE remains interrupted and highly variable in the UK. A collaborative inter-disciplinary approach is required to re-introduce FNE safely in volume across healthcare settings, re-establishing timely endoscopic diagnosis and pre-pandemic levels of patient care.

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Abstract 021: C-reactive Protein Partially Mediates The Inverse Association Between Coffee Consumption And Risk Of Type 2 Diabetes: Findings From The UK Biobank And The Rotterdam Studies

Circulation ◽

10.1161/circ.143.suppl_1.021 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Carolina Ochoa-Rosales ◽

Niels van der Schaft ◽

Kim V Braun ◽

Frederick Ho ◽

Fanny Petermann ◽

...

Keyword(s):

Type 2 Diabetes ◽

Coffee Consumption ◽

Inverse Association ◽

Statistical Regression ◽

Uk Biobank ◽

C Reactive Protein ◽

Coffee Intake ◽

Reactive Protein ◽

The Uk

Background: Coffee intake has been linked to lower type 2 diabetes (T2D) risk. We hypothesized this may be mediated by coffee’s effects on inflammation. Methods: Using participants from the UK Biobank (UKB n=145370) and Rotterdam Study (RS n=7172) cohorts, we studied associations of coffee intake with incident T2D; longitudinally measured insulin resistance (HOMA IR); serum levels of inflammation markers; and the mediating role of inflammation. Statistical regression models were adjusted for sociodemographic, lifestyle and health factors. Results: The median follow up was 7 (UKB) and 9 (RS) years. An increase of one coffee cup/day was associated with 4-6% lower T2D risk (RS HR=0.94 [95% CI 0.90; 0.98]; UKB HR=0.96 [0.94; 0.98]); lower HOMA IR (RS β=-0.017 [-0.024; -0.010]); with lower C reactive protein (CRP) and higher adiponectin (Figure1). Consumers of filtered coffee had the lowest T2D risk (UKB HR=0.88 [0.83; 0.93]). CRP levels mediated 9.6% (UKB) and 3.4% (RS) of the total effect of coffee on T2D (Figure 1). Conclusions: We suggest that coffee’s beneficial effects on lower T2D risk are partially mediated by improvements in systemic inflammation.Figure 1. a CRP and a adiponectin refer to the effect of coffee intake on CRP and adiponectin levels. a CRP RS : β=-0.014 (-0.022; -0.005); UKBB a CRP UKB : β=-0.011 (-0.012; -0.009) and RS a adiponectin : β=0.025 (0.007; 0.042). b CRP and b adiponectin refer to the effect of coffee related levels in CRP and adiponectin on incident T2D, independent of coffee. RS b CRP : HR=1.17 (1.04; 1.31); UKB b CRP : HR=1.45 (1.37; 1.54); and b adiponectin : HR=0.58 (0.32; 0.83). c′ refers to coffee’ effect on T2D going directly or via others mediators. UKB c′ independent of CRP : HR=0.96 (0.94; 0.99); RS c′ independent of CRP : HR=0.94 (0.90; 0.99); and RS c′ independent of CRP+adiponectin : HR=0.90 (0.80; 1.01). Coffee related changes in CRP may partially explain the beneficial link between coffee and T2D, mediating a 3.4% (0.6; 4.8, RS) and 9.6% (5.7; 24.4, UKB). Evidence of mediation was also found for adiponectin.

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The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile

Cancers ◽

10.3390/cancers12071961 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1961 ◽

Cited By ~ 1

Author(s):

Helene Hersvik Aarstad ◽

Gigja Guðbrandsdottir ◽

Karin M. Hjelle ◽

Leif Bostad ◽

Øystein Bruserud ◽

...

Keyword(s):

Cancer Patients ◽

Renal Cancer ◽

Acute Phase ◽

High Serum ◽

Cytokine Profile ◽

Phase Reaction ◽

C Reactive Protein ◽

Reactive Protein ◽

Wide Range ◽

The Impact

High serum levels of the acute phase protein C-reactive protein (CRP) are associated with an adverse prognosis in renal cancer. The acute phase reaction is cytokine-driven and includes a wide range of inflammatory mediators. This overall profile of the response depends on the inducing event and can also differ between patients. We investigated an extended acute phase cytokine profile for 97 renal cancer patients. Initial studies showed that the serum CRP levels had an expected prognostic association together with tumor size, stage, nuclear grading, and Leibovich score. Interleukin (IL)6 family cytokines, IL1 subfamily mediators, and tumor necrosis factor (TNF)α can all be drivers of the acute phase response. Initial studies suggested that serum IL33Rα (the soluble IL33 receptor α chain) levels were also associated with prognosis, although the impact of IL33Rα is dependent on the overall cytokine profile, including seven IL6 family members (IL6, IL6Rα, gp130, IL27, IL31, CNTF, and OSM), two IL1 subfamily members (IL1RA and IL33Rα), and TNFα. We identified a patient subset characterized by particularly high levels of IL6, IL33Rα, and TNFα alongside an adverse prognosis. Thus, the acute phase cytokine reaction differs between renal cancer patients, and differences in the acute phase cytokine profile are associated with prognosis.

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Association of Antioxidants Use with All-Cause and Cause-Specific Mortality: A Prospective Study of the UK Biobank

Antioxidants ◽

10.3390/antiox9121287 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1287

Author(s):

Inken Behrendt ◽

Gerrit Eichner ◽

Mathias Fasshauer

Keyword(s):

Respiratory Disease ◽

Mortality Risk ◽

Cancer Mortality ◽

Primary Objective ◽

Inverse Association ◽

Uk Biobank ◽

Cancer Subtypes ◽

Specific Mortality ◽

The Uk ◽

The Impact

Prospective studies and randomized controlled trials elucidating the impact of antioxidants supplementation on mortality risk are inconclusive. The present analysis determined association between regular antioxidants use and all-cause (primary objective), as well as cause-specific, mortality in 345,626 participants of the UK Biobank cohort using Cox proportional hazard models. All models were adjusted for confounders and multiple testing. Antioxidants users were defined as participants who indicated to regularly use at least one of the following: multivitamins, vitamin C, vitamin E, selenium, and zinc. Median age of antioxidants users (n = 101,159) and non-users (n = 244,467) at baseline was 57 years. During 3.9 million person-years and a median follow-up of 11.5 years, 19,491 deaths occurred. Antioxidants use was not significantly associated with all-cause, cancer, and non-cancer mortality including several cancer and non-cancer subtypes. Interestingly, mortality risk from respiratory disease was significantly 21% lower among antioxidants users as compared to non-users (hazard ratio: 0.79; 95% confidence interval: 0.67, 0.92). In conclusion, the present study findings do not support recommendations for antioxidants supplementation to prevent all-cause, cancer, or non-cancer mortality on a population level. The significant inverse association between antioxidants use and respiratory disease mortality needs further study.

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