Gout and coronavirus disease-19 (COVID-19): the risk of diagnosis and death in the UK Biobank

AbstractBackgroundData on outcomes for people with gout and COVID-19 are extremely few. Our primary objective was to assess whether gout is a risk factor for diagnosis of COVID-19 and death related to COVID-19. The secondary objectives were to test for sex- and drug-specific differences in risk.MethodsWe used data from the UK Biobank that included 15,560 people with gout. Multivariable-adjusted logistic regression was employed in the following analyses using a case-control study design: Analysis A, to test for association between gout and COVID-19 diagnosis (n=459,837); Analysis B, to test for association between gout and death related to COVID-19 in a case-control cohort of people who died or survived with COVID-19 (n=16,336); Analysis C, to test for association between gout and death related to COVID-19 in the entire UK Biobank cohort (n=459,837); Analysis D, to stratify by prescription of urate-lowering therapy (ULT) and colchicine on the risk of death related to COVID-19 in a subset of the UK Biobank cohort with medication data (n=341,398).FindingsGout was associated with diagnosis of COVID-19 in analysis A (OR=1.2 [1.1 ; 1.3]) but not with risk of death in the COVID-19-diagnosed group in analysis B. In analysis C gout associated with risk of death related to COVID-19 in the unadjusted model (OR=3.9 [3.3 ; 4.7]), in Model 1 adjusted for demographic factors (OR=1.8 [1.5 ; 2.1]) and in the fully adjusted Model 2 (OR=1.3 [1.1 ; 1.6]). In Analysis C risk was higher in women than men in Model 1 adjusted for demographic factors (OR=3.5 [2.4 ; 5.0] and OR=1.5 [1.2 ; 1.8], respectively) with the difference maintained after additional adjustment for eight metabolic co-morbidities (ORMen=1.2 [0.9 ; 1.5], ORWomen=1.9 [1.3 ; 2.9]). There were no statistically significant differences in risk of death related to COVID-19 according to prescription of ULT or colchicine.InterpretationGout is a risk factor for death related to COVID-19 using the UK Biobank cohort with an increased risk in women with gout that was also driven by risk factors outside metabolic co-morbidities of gout.Research in contextEvidence before this studyThere are no studies investigating the risk of COVID-19 diagnosis and risk of death with COVID-19 in people with gout.Added value of this studyThe findings provide evidence that gout is a risk factor for diagnosis of COVID-19 and that gout is a risk factor for death with COVID-19, independent of included co-morbidities. Women with gout are at a higher risk of death with COVID-19 than men with gout.Implications of the available evidenceThe new evidence demonstrate that gout is a risk factor for death from COVID-19, particularly in women. This information will inform clinical decision-making in people with gout diagnosed with COVID-19. Future research should focus on replicating these findings, including a focus on understanding key factor(s) explaining the increased risk of death with COVID-19 in women with gout.

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Case-control study of acute renal failure in patients with cystic fibrosis in the UK

Thorax ◽

10.1136/thx.2007.088757 ◽

2008 ◽

Vol 63 (6) ◽

pp. 532-535 ◽

Cited By ~ 71

Author(s):

A Smyth ◽

S Lewis ◽

C Bertenshaw ◽

I Choonara ◽

J McGaw ◽

...

Keyword(s):

Cystic Fibrosis ◽

Renal Failure ◽

Acute Renal Failure ◽

Risk Factor ◽

Case Control Study ◽

Case Control ◽

Increased Risk ◽

Long Term Treatment ◽

The Uk ◽

Control Study

Background:There has been a recent increase in the number of reported cases of acute renal failure (ARF) in cystic fibrosis (CF). A case-control study was conducted to determine the factors which are associated with an increased risk of ARF.Methods:24 cases of confirmed ARF were identified in patients with CF from 20 UK CF centres presenting between 1997 and 2004. Using the UK CF database, sex- and age-matched controls were identified. Risk factors were analysed by conditional logistic regression and Mantel-Haenszel analysis.Results:21 of the 24 patients with ARF had received an aminoglycoside at the time of their episode of ARF or in the preceding week compared with only 3 of 42 controls during the same time period (OR 81.8, 95% CI 4.7 to 1427, p<0.001). In the year before the episode of ARF, significantly more cases than controls had received gentamicin (19/24 cases vs 1/42 controls, p<0.001). The numbers receiving tobramycin were similar (9/24 cases vs 16/42 controls, p = 0.9). A known risk factor for renal impairment (prior renal disease, acute dehydration or long-term treatment with a nephrotoxic drug) was present in 18/24 cases and 7/42 controls (OR 24.0, 95% CI 3.1 to 186.6, p = 0.002).Conclusions:In patients with CF the use of an intravenous aminoglycoside is a risk factor for ARF; gentamicin is more nephrotoxic than tobramycin. Most patients who develop ARF have a risk factor which necessitates withholding aminoglycosides or more closely monitoring their use.

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Gout, rheumatoid arthritis and the risk of death from COVID-19: an analysis of the UK Biobank

10.1101/2020.11.06.20227405 ◽

2020 ◽

Author(s):

Ruth K Topless ◽

Amanda Phipps-Green ◽

Megan Leask ◽

Nicola Dalbeth ◽

Lisa K Stamp ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Population Based ◽

Data Sets ◽

Uk Biobank ◽

Control Cohort ◽

Risk Of Death ◽

Increased Risk ◽

Adjusted Logistic Regression ◽

The Uk

AbstractObjectiveTo assess whether gout and / or rheumatoid arthritis (RA) are risk factors for coronavirus disease 19 (COVID-19) diagnosis. To assess whether gout and / or RA are risk factors for death from COVID-19.MethodsWe used data from the UK Biobank. Multivariate-adjusted logistic regression was employed in the following analyses. Analysis A: to test for association between gout or RA and COVID-19 diagnosis in a population-based cohort (n=473,139). Analysis B: to test for association between gout or RA and death from COVID-19 in a case-control cohort of people who died or survived with COVID-19 (n=2,073). Analysis C: to test for association with gout or RA and death from COVID-19 in a population-based cohort (n=473,139)ResultsNeither RA nor gout associated with COVID-19 diagnosis in analysis A, nor did RA or gout associate with risk of death in the COVID-19-diagnosed group in analysis B. However RA associated with risk of death from COVID-19 using the population-based cohort in analysis C independent of comorbidities and other measured risk factors (OR=1.8 [95% CI 1.2 ; 2.7]). Gout was not associated with death from COVID-19 in the same population-based analysis (OR=1.2 [95% CI 0.9 ; 1.7]).ConclusionsRA and gout are not risk factors for COVID-19-diagnosis. However RA, but not gout, is a risk factor for death from COVID-19 in a population-based analysis using the UK Biobank. These findings require replication in larger data sets that also allow inclusion of a wider range of factors.Key messagesWhat is already known?Information on the risk of death from COVID-19 for people with gout and rheumatoid arthritis is scarce.What does this study add?In a population-based analysis there is an increased risk of death by COVID-19 for people with rheumatoid arthritis independent of co-morbidities, but not gout.The findings need to be replicated in other datasets where the influence of therapies for RA can be tested.How might this impact on clinical practice?Improved clinical management and treatment for RA patients with COVID-19.

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801Apolipoprotein E (APOE) genotype-associated disease risks: a phenome-wide, registry-based, case-control study utilising the UK biobank

International Journal of Epidemiology ◽

10.1093/ije/dyab168.404 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Amanda Lumsden ◽

Anwar Mulugeta ◽

Ang Zhou ◽

Elina Hyppönen

Keyword(s):

Cardiovascular Diseases ◽

Wide Spectrum ◽

Apoe Genotype ◽

Case Control ◽

Uk Biobank ◽

Disease Outcomes ◽

Increased Risk ◽

Disease Associations ◽

The Uk ◽

Apoe Genotypes

Abstract Background The APOE gene has three main alleles; APOE-E2, E3 and E4 (global frequencies: 8%, 78%, 14%) carrying differential risk for conditions such as dementia and cardiovascular disease. Due to the clinical significance of variation at this locus, we explored disease associations of APOE genotypes using a hypothesis-free, phenome-wide association study (PheWAS) approach. Methods Utilising medical and genetic data available from the UK Biobank for 337,484 white British participants aged 37–73 years, we screened for associations between APOE genotypes (E4E4, E3E4, E2E4, E2E3 and E2E2) and ≥825 disease outcomes, using E3E3 as a reference. Results Case-control PheWAS analyses revealed associations with 37 disease outcomes from 17 distinct conditions after multiple test correction. As expected, E4E4 and E3E4 associated with risk of Alzheimer’s disease (p < 10-46 for both), hypercholesterolemia (p < 10-17), and cardiovascular diseases (p < 10-4). Novel findings included E4-associated increased risk of chondrocalcinosis (E4E4), and protection against obesity (E4E4), type 2 diabetes (E4E4, E4E3), and chronic airway obstruction (E4E4; all p ≤ 3.2 × 10-4). Notably, E2E2 homozygosity augmented risks of peripheral vascular diseases, and cervical disorders (p ≤ 1·9 × 10-5). Conclusions PheWAS assessment of APOE-associated risk for a wide spectrum of diseases amongst this large, white British population, detected well-established, and novel APOE-disease associations warranting further validation. Key messages While APOE-E4 is risky for Alzheimer’s, and cardiovascular diseases, it may be protective against some metabolic conditions. While the E2 allele is often considered beneficial, homozygosity-associated risks may contribute to its relatively low prevalence.

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Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data

Human Genomics ◽

10.1186/s40246-021-00306-7 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Jianchang Hu ◽

Cai Li ◽

Shiying Wang ◽

Ting Li ◽

Heping Zhang

Keyword(s):

Genetic Variants ◽

Genetic Factors ◽

Genome Wide Association Study ◽

Individual Risk ◽

Uk Biobank ◽

Risk Of Death ◽

Genome Wide ◽

A Genome ◽

Increased Risk ◽

The Uk

Abstract Background The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors. Methods In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations. Results We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2. Conclusions Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.

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Social isolation and loneliness as risk factors for myocardial infarction, stroke and mortality: UK Biobank cohort study of 479 054 men and women

Heart ◽

10.1136/heartjnl-2017-312663 ◽

2018 ◽

Vol 104 (18) ◽

pp. 1536-1542 ◽

Cited By ~ 52

Author(s):

Christian Hakulinen ◽

Laura Pulkki-Råback ◽

Marianna Virtanen ◽

Markus Jokela ◽

Mika Kivimäki ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Social Isolation ◽

Uk Biobank ◽

Risk Of Death ◽

Increased Risk ◽

History Of ◽

The Uk ◽

Adjusted Model ◽

Conventional Risk Factors

ObjectiveTo examine whether social isolation and loneliness (1) predict acute myocardial infarction (AMI) and stroke among those with no history of AMI or stroke, (2) are related to mortality risk among those with a history of AMI or stroke, and (3) the extent to which these associations are explained by known risk factors or pre-existing chronic conditions.MethodsParticipants were 479 054 individuals from the UK Biobank. The exposures were self-reported social isolation and loneliness. AMI, stroke and mortality were the outcomes.ResultsOver 7.1 years, 5731 had first AMI, and 3471 had first stroke. In model adjusted for demographics, social isolation was associated with higher risk of AMI (HR 1.43, 95% CI 1.3 to –1.55) and stroke (HR 1.39, 95% CI 1.25 to 1.54). When adjusted for all the other risk factors, the HR for AMI was attenuated by 84% to 1.07 (95% CI 0.99 to 1.16) and the HR for stroke was attenuated by 83% to 1.06 (95% CI 0.96 to 1.19). Loneliness was associated with higher risk of AMI before (HR 1.49, 95% CI 1.36 to 1.64) but attenuated considerably with adjustments (HR 1.06, 95% CI 0.96 to 1.17). This was also the case for stroke (HR 1.36, 95% CI 1.20 to 1.55 before and HR 1.04, 95% CI 0.91 to 1.19 after adjustments). Social isolation, but not loneliness, was associated with increased mortality in participants with a history of AMI (HR 1.25, 95% CI 1.03 to 1.51) or stroke (HR 1.32, 95% CI 1.08 to 1.61) in the fully adjusted model.ConclusionsIsolated and lonely persons are at increased risk of AMI and stroke, and, among those with a history of AMI or stroke, increased risk of death. Most of this risk was explained by conventional risk factors.

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Genetic risk factors for death with SARS-CoV-2 from the UK Biobank

10.1101/2020.07.01.20144592 ◽

2020 ◽

Cited By ~ 1

Author(s):

Chang Lu ◽

Rihab Gam ◽

Arun Prasad Pandurangan ◽

Julian Gough

Keyword(s):

Risk Factors ◽

Genetic Risk ◽

Genetic Risk Factors ◽

Uk Biobank ◽

Factors Affecting ◽

Risk Of Death ◽

Global Pandemic ◽

Risk Variants ◽

Increased Risk ◽

The Uk

AbstractWe present here genetic risk factors for survivability from infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for coronavirus disease 19 (COVID-19). At the time of writing it is too early to determine comprehensively and without doubt all risk factors, but there is an urgency due to the global pandemic crisis that merits this early analysis. We have nonetheless discovered 5 novel risk variants in 4 genes, discovered by examining 193 deaths from 1,412 confirmed infections in a group of 5,871 UK Biobank participants tested for the virus. We also examine the distribution of these genetic variants across broad ethnic groups and compare it to data from the UK Office of National Statistics for increased risk of death from SARS-CoV-2. We confidently identify the gene ERAP2 with a high-risk variant, as well as three other genes of potential interest. Although mostly rare, a common theme of genetic risk factors affecting survival might be the inability to launch or modulate an effective immune and stress response to infection from the SARS-CoV-2 virus.

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Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort

Cancers ◽

10.3390/cancers13071514 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1514

Author(s):

Shing Fung Lee ◽

Maja Nikšić ◽

Bernard Rachet ◽

Maria-Jose Sanchez ◽

Miguel Angel Luque-Fernandez

Keyword(s):

Cancer Patients ◽

Socioeconomic Inequalities ◽

Uk Biobank ◽

Incident Cancer ◽

Increased Risk ◽

Exposure Variable ◽

Independent Risk Factors ◽

The Uk ◽

Deprived Areas

We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.

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Routine use of immunosuppressants is associated with mortality in hospitalised patients with COVID-19

Therapeutic Advances in Drug Safety ◽

10.1177/2042098620985690 ◽

2021 ◽

Vol 12 ◽

pp. 204209862098569

Author(s):

Phyo K. Myint ◽

Ben Carter ◽

Fenella Barlow-Pay ◽

Roxanna Short ◽

Alice G. Einarsson ◽

...

Keyword(s):

Medical Attention ◽

Close Monitoring ◽

Plain Language ◽

Discharge Data ◽

Specific Patient ◽

Risk Of Death ◽

Hospitalised Patients ◽

Increased Risk ◽

The Uk ◽

The Impact

Background: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. Methods: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. Results: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62–83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01–2.88 (14-day mortality). There also appeared to be a dose–response relationship. Conclusion: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. Plain Language Summary Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.

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Gout, Rheumatoid Arthritis, and the Risk of Death Related to Coronavirus Disease 2019: An Analysis of the UK Biobank

ACR Open Rheumatology ◽

10.1002/acr2.11252 ◽

2021 ◽

Author(s):

Ruth K. Topless ◽

Amanda Phipps‐Green ◽

Megan Leask ◽

Nicola Dalbeth ◽

Lisa K. Stamp ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Uk Biobank ◽

Risk Of Death ◽

The Uk

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Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

Psychological Medicine ◽

10.1017/s0033291718000454 ◽

2018 ◽

Vol 49 (15) ◽

pp. 2499-2504 ◽

Cited By ~ 7

Author(s):

Valentina Escott-Price ◽

Daniel J. Smith ◽

Kimberley Kendall ◽

Joey Ward ◽

George Kirov ◽

...

Keyword(s):

Environmental Exposure ◽

Copy Number Variants ◽

Season Of Birth ◽

Uk Biobank ◽

Month Of Birth ◽

Risk Alleles ◽

Gene Environment ◽

Increased Risk ◽

The Uk ◽

Pathogenic Process

AbstractBackgroundThere is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.MethodsHere we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.ResultsNeither genetic measure was associated with season or month of birth within the UKBB sample.ConclusionsAs our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.

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