Publications
886 results found
Loo RL, Chan Q, Antti H, et al., 2020, Manuscript Strategy for improved characterisation of human metabolic phenotypes using a COmbined Multiblock Principal components Analysis with Statistical Spectroscopy (COMPASS), Bioinformatics, Vol: 36, Pages: 5229-5236, ISSN: 1367-4803
MOTIVATION: Large-scale population omics data can provide insight into associations between gene-environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. RESULTS: Here we present an interactive software pipeline for exploratory analyses of population-based nuclear magnetic resonance spectral data using a COmbined Multiblock Principal components Analysis with Statistical Spectroscopy (COMPASS) within the R-library hastaLaVista framework. Principal component analysis models are generated for a sequential series of spectral regions (blocks) to provide more granular detail defining sub-populations within the dataset. Molecular identification of key differentiating signals is achieved by implementing statistical correlation spectroscopy (STOCSY) on the full spectral data to define feature patterns. Finally, the distributions of cross-correlation of the reference patterns across the spectral dataset is used to provide population statistics for identifying underlying features arising from drug intake, latent diseases and diet. The COMPASS thus provides an efficient semi-automated approach for screening population datasets. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/cheminfo/COMPASS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Riley S, Ainslie KEC, Eales O, et al., 2020, High and increasing prevalence of SARS-CoV-2 swab positivity in England during end September beginning October 2020: REACT-1 round 5 updated report
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-1 is quantifying prevalence of SARS-CoV-2 infection among random samples of the population in England based on PCR testing of self-administered nose and throat swabs. Here we report results from the fifth round of observations for swabs collected from the 18th September to 5th October 2020. This report updates and should be read alongside our round 5 interim report.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Representative samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 175,000 people at each round. Prevalence of PCR-confirmed SARS-CoV-2 infection, estimation of reproduction number (R) and time trends between and within rounds using exponential growth or decay models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>175,000 volunteers tested across England between 18th September and 5th October. Findings show a national prevalence of 0.60% (95% confidence interval 0.55%, 0.71%) and doubling of the virus every 29 (17, 84) days in England corresponding to an estimated national R of 1.16 (1.05, 1.27). These results correspond to 1 in 170 people currently swab-positive for the virus and approximately 45,000 new infections each day. At regional level, the highest prevalence is in the North West, Yorkshire and The Humber and the North East with strongest regional growth in North West, Yorkshire and The Humber and West Midlands.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Rapid growth has led to high prevalence of SARS-CoV-2 virus in England, with highest rates in the North of England. Prevalence has increased in all age groups, including those at highest risk. Improved compliance with existing policy and, as necessar
Huang J, Zuber V, Matthews P, et al., 2020, Sleep, major depressive disorder and Alzheimer’s disease: a Mendelian randomisation study, Neurology, Vol: 95, ISSN: 0028-3878
ObjectiveTo explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer’s disease (AD).MethodsWe conducted bi-directional two-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N=446,118), the Psychiatric Genomics Consortium (N=18,759), and the International Genomics of Alzheimer’s Project (N=63,926). We used the inverse variance weighted Mendelian randomisation method to estimate causal effects, and weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects. ResultsWe found that higher risk of AD was significantly associated with being a “morning person” (odds ratio (OR)=1.01, P=0.001), shorter sleep duration (self-reported: β=-0.006, P=1.9×10-4; accelerometer-based: β=-0.015, P=6.9×10-5), less likely to report long sleep (β=-0.003, P=7.3×10-7), earlier timing of the least active 5 hours (β=-0.024, P=1.7×10-13), and a smaller number of sleep episodes (β=-0.025, P=5.7×10-14) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR=0.99, P=7×10-13). However, we did not find evidence either that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. ConclusionWe found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.
Riley S, Ainslie KEC, Eales O, et al., 2020, High prevalence of SARS-CoV-2 swab positivity in England during September 2020: interim report of round 5 of REACT-1 study, Publisher: Cold Spring Harbor Laboratory Press
Background REACT-1 is a community survey of PCR confirmed swab-positivity for SARS-CoV-2 among random samples of the population in England. This interim report includes data from the fifth round of data collection currently underway for swabs sampled from the 18th to 26th September 2020.Methods Repeated cross-sectional surveys of random samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 160,000 people in each round of data collection. Collection of self-administered nose and throat swab for PCR and questionnaire data. Prevalence of swab-positivity by round and by demographic variables including age, sex, region, ethnicity. Estimation of reproduction number (R) between and within rounds, and time trends using exponential growth or decay model. Assessment of geographical clustering based on boundary-free spatial model.Results Over the 9 days for which data are available, we find 363 positives from 84,610 samples giving a weighted prevalence to date of 0.55% (0.47%, 0.64%) in round 5. This implies that 411,000 (351,000, 478,000) people in England are virus-positive under the assumption that the swab assay is 75% sensitive. Using data from the most recent two rounds, we estimate a doubling time of 10.6 (9.4, 12.0) days covering the period 20th August to 26th September, corresponding to a reproduction number R of 1.47 (1.40, 1.53). Using data only from round 5 we estimate a reproduction number of 1.06 (0.74, 1.46) with probability of 63% that R is greater than 1. Between rounds 4 and 5 there was a marked increase in unweighted prevalence at all ages. In the most recent data, prevalence was highest in the 18 to 24 yrs age group at 0.96% (0.68%, 1.36%). At 65+ yrs prevalence increased 7-fold between rounds 4 and 5 from 0.04% (0.03%, 0.07%) to 0.29% (0.23%, 0.37%). Prevalence increased in all regions between rounds 4 and 5, giving the highest unweighted prevalence in round 5 in the North West at 0.86% (0.69%, 1.06%). In Lond
Aljuraiban GS, Pertiwi K, Stamler J, et al., 2020, Potato consumption, by preparation method and meal quality, with blood pressure and body mass index: The INTERMAP study, Clinical Nutrition, Vol: 39, Pages: 3042-3048, ISSN: 0261-5614
BACKGROUND AND AIMS: Previous studies have reported associations between higher potato intake and higher blood pressure (BP) and/or risk of hypertension and obesity. These studies rarely considered preparation methods of potatoes, overall dietary pattern or the nutrient quality of the meals. These factors may affect the association of potato intake with BP and body mass index (BMI). This study investigated potato consumption by amount, type of processing, overall dietary pattern, and nutrient quality of the meals in relation to BP and BMI. METHODS: Cross-sectional analyses were conducted among 2696 participants aged 40-59 y in the US and UK samples of the International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Nutrient quality of individual food items and the overall diet was assessed with the Nutrient-Rich Foods (NRF) index. RESULTS: No associations with BP or BMI were found for total potato intake nor for boiled, mashed, or baked potatoes or potato-based mixed dishes. In US women, higher intake of fried potato was associated with 2.29 mmHg (95% CI: 0.55, 3.83) higher systolic BP and with 1.14 mmHg (95% CI: 0.10, 2.17) higher diastolic BP, independent of BMI. Higher fried potato consumption was directly associated with a +0.86 kg/m2 difference in BMI (95% CI: 0.24, 1.58) in US women. These associations were not found in men. Higher intakes of fried potato meals with a lower nutritional quality (NRF index≤ 2) were positively associated with systolic (3.88 mmHg; 95% CI: 2.63, 5.53) and diastolic BP (1.62 mmHg; 95% CI: 0.48, 2.95) in US women. No associations with BP were observed for fried potato meals with a higher nutritional quality (NRF index> 2). CONCLUSIONS: Fried potato was directly related to BP and BMI in women, but non-fried potato was not. Poor-nutrient quality meals were associated with intake of fried potatoes and higher BP, suggesting that accompanied dietary choices are key mediators of
Chadeau M, Bodinier B, Elliott J, et al., 2020, Risk factors for positive and negative COVID-19 tests: a cautious and in-depth analysis of UK Biobank data, International Journal of Epidemiology, Vol: 49, Pages: 1454-1467, ISSN: 0300-5771
BackgroundThe recent COVID-19 outbreak has generated an unprecedented public health crisis, with millions of infections and hundreds of thousands of deaths worldwide. Using hospital-based or mortality data, several COVID-19 risk factors have been identified, but these may be confounded or biased.MethodsUsing SARS-CoV-2 infection test data (N=4,509 tests; 1,325 positive) from Public Health England, linked to the UK Biobank study, we explored the contribution of demographic, social, health risk, medical, and environmental factors to COVID-19 risk. We used multivariable and penalised logistic regression models for the risk of (i) being tested, (ii) testing positive/negative in the study population and, adopting a test negative design, (iv) the risk of testing positive within the tested population.ResultsIn the fully adjusted model, variables independently associated with the risk of being tested for COVID-19 with OR >1.05 were: male sex; Black ethnicity; social disadvantage (as measured by education, housing and income); occupation (healthcare worker, retired, unemployed); ever smoker; severely obese; comorbidities; and greater exposure to PM2.5-absorbance. Of these, only male sex, non-White ethnicity, lower educational attainment, and none of the comorbidities or health risk factors, were associated with testing positive among tested individuals.ConclusionsWe adopted a careful and exhaustive approach within a large population-based cohort, which enabled us to triangulate evidence linking, male sex, lower educational attainment, non-White ethnicity with the risk of COVID-19. The elucidation of the joint and independent effects of these factors is a high-priority area for further research to inform on COVID-19 natural history.
Allen N, Arnold M, Parish S, et al., 2020, 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, Vol: 5, Pages: 1-18, ISSN: 2398-502X
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
Riley S, Ainslie KEC, Eales O, et al., 2020, Resurgence of SARS-CoV-2 in England: detection by community antigen surveillance
<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Based on cases and deaths, transmission of SARS-CoV-2 in England peaked in late March and early April 2020 and then declined until the end of June. Since the start of July, cases have increased, while deaths have continued to decrease.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We report results from 594,000 swabs tested for SARS-CoV-2 virus obtained from a representative sample of people in England over four rounds collected regardless of symptoms, starting in May 2020 and finishing at the beginning of September 2020. Swabs for the most recent two rounds were taken between 24th July and 11th August and for round 4 between 22nd August and 7th September. We estimate weighted overall prevalence, doubling times between and within rounds and associated reproduction numbers. We obtained unweighted prevalence estimates by sub-groups: age, sex, region, ethnicity, key worker status, household size, for which we also estimated odds of infection. We identified clusters of swab-positive participants who were closer, on average, to other swab-positive participants than would be expected.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Over all four rounds of the study, we found that 72% (67%, 76%) of swab-positive individuals were asymptomatic at the time of swab and in the week prior. The epidemic declined between rounds 1 and 2, and rounds 2 and 3. However, the epidemic was increasing between rounds 3 and 4, with a doubling time of 17 (13, 23) days corresponding to an R value of 1.3 (1.2, 1.4). When analysing round 3 alone, we found that the epidemic had started to grow again with 93% probability. Using only the most recent round 4 data, we estimated a doubling time of 7.7 (5.5, 12.7) days, corresponding to an R value of 1.7 (1.4, 2.0). Cy
Vuckovic D, Bao EL, Akbari P, et al., 2020, The polygenic and monogenic basis of blood traits and diseases, Cell, Vol: 182, Pages: 1214-1231.e11, ISSN: 0092-8674
Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.
Chen M-H, Raffield LM, Mousas A, et al., 2020, Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations, CELL, Vol: 182, Pages: 1198-1213.E14, ISSN: 0092-8674
Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10 −9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.
Graham N, Junghans C, Downes R, et al., 2020, SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes, Journal of Infection, Vol: 81, Pages: 411-419, ISSN: 0163-4453
OBJECTIVES: To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents. METHODS: An outbreak investigation involving 394 residents and 70 staff, was carried out in 4 nursing homes affected by COVID-19 outbreaks in central London. Two point-prevalence surveys were performed one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing. RESULTS: Overall, 26% (95% CI 22 to 31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70 to 336) compared with previous years. Systematic testing identified 40% (95% CI 35 to 46) of residents as positive for SARS-CoV-2, and of these 43% (95% CI 34 to 52) were asymptomatic and 18% (95% CI 11 to 24) had only atypical symptoms; 4% (95% CI -1 to 9) of asymptomatic staff also tested positive. CONCLUSIONS: The SARS-CoV-2 outbreak in four UK nursing homes was associated with very high infection and mortality rates. Many residents developed either atypical or no discernible symptoms. A number of asymptomatic staff members also tested positive, suggesting a role for regular screening of both residents and staff in mitigating future outbreaks.
Kaura A, Sterne J, Trickey A, et al., 2020, Invasive versus non-invasive management of elderly patients with non-ST elevation myocardial infarction: cohort study based on routine clinical data, The Lancet, Vol: 396, Pages: 623-634, ISSN: 0140-6736
BackgroundPrevious trials suggest lower long-term mortality after invasive rather than non-invasive management among patients with non-ST elevation myocardial infarction (NSTEMI), but these excluded very elderly patients.MethodsWe estimated the effect of invasive versus non-invasive management within 3 days of peak troponin on survival in NSTEMI patients aged ≥80 years, using routine clinical data collected during 2010–2017 (NIHR Health Informatics Collaborative). Propensity scores based on pre-treatment variables were derived using logistic regression; patients with high probabilities of non-invasive or invasive management were excluded. Patients who died within 3 days without receiving invasive management were assigned to the invasive or non-invasive management groups based on their propensity scores, to mitigate immortal time bias. We estimated mortality hazard ratios comparing invasive with non-invasive management, and also compared rates of hospital admission for heart failure.FindingsOf 1976 patients with NSTEMI, 101 died within 3 days of their peak troponin, whilst 375 were excluded because of extreme propensity scores. The remaining 1500 patients (56% non-invasive management) had a median age 86 (IQR 82-89) years. During median follow-up of 3.0 (IQR 1.2-4.8) years, there were 613 (41%) deaths. Using inverse probability weighting, adjusted cumulative 5-year mortality was 36% and 55% in the invasive and non-invasive management groups, respectively. The mortality hazard ratio comparing invasive with non-invasive management was 0.64 (95% CI 0.52-0.79) after multivariable adjustment for clinical characteristics and propensity score and inclusion of patients who died within three days. Invasive management was associated with lower incidence of hospital admissions for heart failure (adjusted rate ratio compared with non-invasive management 0.67, 95% CI 0.48–0.93).
Atchison C, Pristerà P, Cooper E, et al., 2020, Usability and acceptability of home-based self-testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies for population surveillance, Clinical Infectious Diseases, Vol: 2020, Pages: 1-10, ISSN: 1058-4838
BACKGROUND: This study assesses acceptability and usability of home-based self-testing for SARS-CoV-2 antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10,600 and 3,800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8,693/8,754) of LFIA1 and 98.4% (2,911/2,957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSION: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.
Chatzidiakou L, Krause A, Han Y, et al., 2020, Using low-cost sensor technologies and advanced computational methods to improve dose estimations in health panel studies: results of the AIRLESS project, Journal of Exposure Science and Environmental Epidemiology, Vol: 30, Pages: 981-989, ISSN: 1559-0631
BackgroundAir pollution epidemiology has primarily relied on fixed outdoor air quality monitoring networks and static populations.MethodsTaking advantage of recent advancements in sensor technologies and computational techniques, this paper presents a novel methodological approach that improves dose estimations of multiple air pollutants in large-scale health studies. We show the results of an intensive field campaign that measured personal exposures to gaseous pollutants and particulate matter of a health panel of 251 participants residing in urban and peri-urban Beijing with 60 personal air quality monitors (PAMs). Outdoor air pollution measurements were collected in monitoring stations close to the participants’ residential addresses. Based on parameters collected with the PAMs, we developed an advanced computational model that automatically classified time-activity-location patterns of each individual during daily life at high spatial and temporal resolution.ResultsApplying this methodological approach in two established cohorts, we found substantial differences between doses estimated from outdoor and personal air quality measurements. The PAM measurements also significantly reduced the correlation between pollutant species often observed in static outdoor measurements, reducing confounding effects.ConclusionsFuture work will utilise these improved dose estimations to investigate the underlying mechanisms of air pollution on cardio-pulmonary health outcomes using detailed medical biomarkers in a way that has not been possible before.
Flower B, Brown JC, Simmons B, et al., 2020, Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 sero-prevalence survey, Thorax, Vol: 75, Pages: 1082-1088, ISSN: 0040-6376
BackgroundAccurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.MethodsSensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by RT-PCR and were ≥21d from symptom-onset. In phase I we evaluated five LFIAs in clinic (with finger-prick) and laboratory (with blood and sera) in comparison to a) PCR-confirmed infection and b) presence of SARS-CoV-2 antibodies on two “in-house” ELISAs. Specificity analysis was performed on 500 pre-pandemic sera. In phase II, six additional LFIAs were assessed with serum.Findings95% (95%CI [92.2, 97.3]) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8/11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21%-92% vs PCR-confirmed cases and 22%-96% vs composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2% - 99.8%).InterpretationLFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI [97.1, 99.4])), moderate sensitivity (84.4% with fingerprick (95%CI [70.5, 93.5])), and moderate concordance, suitable for seroprevalence surveys.
Riley S, Ainslie KEC, Eales O, et al., 2020, Transient dynamics of SARS-CoV-2 as England exited national lockdown
<jats:title>Abstract</jats:title><jats:p>Control of the COVID-19 pandemic requires a detailed understanding of prevalence of SARS-CoV-2 virus in the population. Case-based surveillance is necessarily biased towards symptomatic individuals and sensitive to varying patterns of reporting in space and time. The real-time assessment of community transmission antigen study (REACT-1) is designed to overcome these limitations by obtaining prevalence data based on a nose and throat swab RT-PCR test among a representative community-based sample in England, including asymptomatic individuals. Here, we describe results comparing rounds 1 and 2 carried out during May and mid June / early July 2020 respectively across 315 lower tier local authority areas. In round 1 we found 159 positive samples from 120,620 tested swabs while round 2 there were 123 positive samples from 159,199 tested swabs, indicating a downwards trend in prevalence from 0.13% (95% CI, 0.11%, 0.15%) to 0.077% (0.065%, 0.092%), a halving time of 38 (28, 58) days, and an R of 0.89 (0.86, 0.93). The proportion of swab-positive participants who were asymptomatic at the time of sampling increased from 69% (61%, 76%) in round 1 to 81% (73%, 87%) in round 2. Although health care and care home workers were infected far more frequently than other workers in round 1, the odds were markedly reduced in round 2. Age patterns of infection changed between rounds, with a reduction by a factor of five in prevalence in 18 to 24 year olds. Our data were suggestive of increased risk of infection in Black and Asian (mainly South Asian) ethnicities. Using regional and detailed case location data, we detected increased infection intensity in and near London. Under multiple sensitivity analyses, our results were robust to the possibility of false positives. At the end of the initial lockdown in England, we found continued decline in prevalence and a shift in the pattern of infection by age and occupation. Community-b
Garcia Perez I, Posma JM, Serrano Contreras JI, et al., 2020, Identifying unknown metabolites using NMR-based metabolic profiling techniques, Nature Protocols, Vol: 15, Pages: 2538-2567, ISSN: 1750-2799
Metabolic profiling of biological samples provides important insights into multiple physiological and pathological processes, but is hindered by a lack of automated annotation and standardised methods for structure elucidation of candidate disease biomarkers. Here, we describe a system for identifying molecular species derived from NMR spectroscopy based metabolic phenotyping studies, with detailed info on sample preparation, data acquisition, and data modelling. We provide eight different modular workflows to be followed in a recommended sequential order according to their level of difficulty. This multi-platform system involves the use of statistical spectroscopic tools such as STOCSY, STORM and RED-STORM to identify other signals in the NMR spectra relating to the same molecule. It also utilizes 2D-NMR spectroscopic analysis, separation and pre-concentration techniques, multiple hyphenated analytical platforms and data extraction from existing databases. The complete system, using all eight workflows, would take up to a month, as it includes multidimensional NMR experiments that require prolonged experiment times. However, easier identification cases using fewer steps would take two or three days. This approach to biomarker discovery is efficient, cost-effective and offers increased chemical space coverage of the metabolome, resulting in faster and more accurate assignment of NMR-generated biomarkers arising from metabolic phenotyping studies. Finally, it requires basic understanding of Matlab in order to perform statistical spectroscopic tools and analytical skills to perform Solid Phase Extraction, LC-fraction collection, LC-NMR-MS and 1D and 2D NMR experiments.
Jenkins R, Shen C, Dumontheil I, et al., 2020, Social networking site use in young adolescents: association with health-related quality of life and behavioural difficulties, Computers in Human Behavior, Vol: 109, Pages: 1-10, ISSN: 0747-5632
Despite Social Networking Sites (SNS) having a minimum age of 13, younger adolescents are using them. In this study, we examine self-reported overall SNS use and SNS use if awake at night in relation to Health-Related Quality of Life (HRQOL, measured by KIDSCREEN-10) and behaviour (measured by Strengths and DifficultiesQuestionnaire, SDQ) in 5229 adolescents aged 11–12 in the Study of Cognition, Adolescents and Mobile Phones (SCAMP) cohort. Two-thirds of the study population used SNS. Weekday and weekend SNS use on mobile phones and other devices was significantly associated with lower HRQOL in females (all p-values for linear trend < 0.01) but not males. Using SNS if awake at night was also significantly associated with lower HRQOL in females (adjustedβ-coefficient - 2.20 (95% CI - 3.18, - 1.22)). Higher SNS use on mobile phones and other devices was associated with increased behavioural difficulties in both genders (p-value for trend < 0.001). Similarly, SNS useif awake at night was associated with greater behavioural difficulties (adjusted β-coefficient 2.54 (95% CI 2.09, 2.98)). We recommend further longitudinal research in this area in order have a better understanding of the direction of relationships between SNS and wellbeing and behaviour in adolescents.
Zhang Y, Elliott P, Toledano M, et al., 2020, The Consortium on Vulnerability to Externalising Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India, Molecular Psychiatry, Vol: 25, Pages: 1618-1630, ISSN: 1359-4184
The global burden of disease attributable to externalising disorders such as alcohol misusecalls urgently for effective prevention and intervention. As our current knowledge is mainlyderived from high-income countries such in Europe and North-America, it is difficult toaddress the wider socio-cultural, psychosocial context, and genetic factors in which risk andresilience are embedded in low- and medium-income countries. c-VEDA was established asthe first and largest India-based multi-site cohort investigating the vulnerabilities for thedevelopment of externalising disorders, addictions, and other mental health problems. Usinga harmonised data collection plan coordinated with multiple cohorts in China, USA, andEurope, baseline data were collected from 7 study sites between November 2016 and May2019. 9010 participants between the ages of 6 and 23 were assessed during this time, amongstwhich 1278 participants underwent more intensive assessments including MRI scans. Bothwaves of follow-ups have started according to the accelerated cohort structure with plannedmissingness design. Here we present descriptive statistics on several key domains ofassessments, and the full baseline dataset will be made accessible for researchers outside theconsortium in September 2019. More details can be found on our website [cveda.org].
Georgakis MK, Gill D, Webb AJS, et al., 2020, Genetically determined blood pressure, antihypertensive drug classes and risk of stroke subtypes, Neurology, Vol: 95, Pages: e353-361, ISSN: 0028-3878
Objective: We employed Mendelian Randomization to explore whether the effects of blood pressure (BP) and BP lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from a GWAS on 757,601 individuals. Applying two-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of WMH.Results: Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not beta blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for CCBs showed particularly strong associations with small vessel stroke and the related radiological phenotype of WMH.Conclusions: This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.
Gill D, Zuber V, Dawson J, et al., 2020, Risk factors mediating the effect of body-mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Higher body-mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits and smoking is not fully understood.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, MR mediation analysis was performed to investigate the degree to which genetically predicted systolic blood pressure (SBP), diabetes, lipid traits and smoking mediated an effect of genetically predicted BMI and WHR on risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The 49% (95% confidence interval [CI] 39%-60%) increased risk of CAD conferred per 1-standard deviation increase in genetically predicted BMI attenuated to 34% (95% CI 24%-45%) after adjusting for genetically predicted SBP, to 27% (95% CI 17%-37%) after adjusting for genetically predicted diabetes, to 47% (95% CI 36%-59%) after adjusting for genetically predicted lipids, and to 46% (95% CI 34%-58%) after adjusting for genetically predicted smoking. Adjusting for all the mediators together, the increased risk attenuated to 14% (95% CI 4%-26%). A similar pattern of attenuation was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcomes.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Measures to reduce obesity will lower risk of cardiovascular disease primarily by impacting on downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongs
Riley S, Ainslie KEC, Eales O, et al., 2020, Community prevalence of SARS-CoV-2 virus in England during May 2020: REACT study
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>England has experienced one of the highest rates of confirmed COVID-19 mortality in the world. SARS-CoV-2 virus has circulated in hospitals, care homes and the community since January 2020. Our current epidemiological knowledge is largely informed by clinical cases with far less understanding of community transmission.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The REal-time Assessment of Community Transmission (REACT) study is a nationally representative prevalence survey of SARS-CoV-2 virus swab-positivity in the community in England. We recruited participants regardless of symptom status.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We found 159 positives from 120,610 swabs giving an average prevalence of 0.13% (95% CI: 0.11%,0.15%) from 1st May to 1st June 2020. We showed decreasing prevalence with a halving time of 8.6 (6.2, 13.6) days, implying an overall reproduction number R of 0.57 (0.45, 0.72). Adults aged 18 to 24 yrs had the highest swab-positivity rates, while those >64 yrs had the lowest. Of the 126 participants who tested positive with known symptom status in the week prior to their swab, 39 reported symptoms while 87 did not, giving an estimate that 69% (61%,76%) of people were symptom-free for the 7 days prior testing positive in our community sample. Symptoms strongly associated with swab-positivity were: nausea and/or vomiting, diarrhoea, blocked nose, loss of smell, loss of taste, headache, chills and severe fatigue. Recent contact with a known COVID-19 case was associated with odds of 24 (16, 38) for swab-positivity. Compared with non-key workers, odds of swab-positivity were 7.7 (2.4, 25) among care home (long-term care facilities) workers and 5.2 (2.9, 9.3) among health care workers. However, some
Elliott P, Muller DC, Schneider-Luftman D, et al., 2020, Estimated 24-hour urinary sodium excretion and incident cardiovascular disease and mortality among 398 628 individuals in UK biobank., Hypertension, Vol: 76, Pages: 1-9, ISSN: 0194-911X
We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40-69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01-1.10) and 0.96 (0.92-1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.
Cai Y, Hansell AL, Granell R, et al., 2020, Prenatal, early-life and childhood exposure to air pollution and lung function: the ALSPAC cohort, American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 112-123, ISSN: 1073-449X
RATIONALE: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health. OBJECTIVES: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy and childhood in a UK population-based birth cohort. METHODS: Individual exposures to source-specific particulate matter with diameter ≤10µm (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993) and up to age 15 years (1991-2008) were examined in relation to %predicted Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at ages 8(N=5,276) and 15(N=3,446) years, usinglinear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods. MEASUREMENTS AND MAIN RESULTS: We did not find clear evidence for a sensitive exposure period for PM10 from road-traffic: at age 8 years, 1µg/m3 higher exposure during the first trimester was associated with lower %predicted of FEV1(-0.826, 95%CI:-1.357 to -0.296) and FVC(-0.817, 95%CI:-1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower %predicted of FVC (-1.312, 95%CI: -2.100 to -0.525). At age 15 years, no adverse associations were seen with lung function. CONCLUSIONS: Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.
Posma JM, Garcia Perez I, Frost G, et al., 2020, Nutriome-metabolome relationships provide insights into dietary intake and metabolism, Nature Food, Vol: 1, Pages: 426-436, ISSN: 2662-1355
Dietary assessment traditionally relies on self-reported data which are often inaccurate and may result in erroneous diet-disease risk associations. We illustrate how urinary metabolic phenotyping can be used as alternative approach for obtaining information on dietary patterns. We used two multi-pass 24-hr dietary recalls, obtained on two occasions on average three weeks apart, paired with two 24-hr urine collections from 1,848 U.S. individuals; 67 nutrients influenced the urinary metabotype measured with ¹H-NMR spectroscopy characterized by 46 structurally identified metabolites. We investigated the stability of each metabolite over time and showed that the urinary metabolic profile is more stable within individuals than reported dietary patterns. The 46 metabolites accurately predicted healthy and unhealthy dietary patterns in a free-living U.S. cohort and replicated in an independent U.K. cohort. We mapped these metabolites into a host-microbial metabolic network to identify key pathways and functions. These data can be used in future studies to evaluate how this set of diet-derived, stable, measurable bioanalytical markers are associated with disease risk. This knowledge may give new insights into biological pathways that characterize the shift from a healthy to unhealthy metabolic phenotype and hence give entry points for prevention and intervention strategies.
Tettamanti G, Auvinen A, Åkerstedt T, et al., 2020, Long-term effect of mobile phone use on sleep quality: results from the cohort study of mobile phone use and health (COSMOS), Environment International, Vol: 140, Pages: 1-9, ISSN: 0160-4120
BACKGROUND: Effects of radiofrequency electromagnetic field exposure (RF-EMF) from mobile phone use on sleep quality has mainly been investigated in cross-sectional studies. The few previous prospective cohort studies found no or inconsistent associations, but had limited statistical power and short follow-up. In this large prospective cohort study, our aim was to estimate the effect of RF-EMF from mobile phone use on different sleep outcomes. MATERIALS AND METHODS: The study included Swedish (n = 21,049) and Finnish (n = 3120) participants enrolled in the Cohort Study of Mobile Phone Use and Health (COSMOS) with information about operator-recorded mobile phone use at baseline and sleep outcomes both at baseline and at the 4-year follow-up. Sleep disturbance, sleep adequacy, daytime somnolence, sleep latency, and insomnia were assessed using the Medical Outcome Study (MOS) sleep questionnaire. RESULTS: Operator-recorded mobile phone use at baseline was not associated with most of the sleep outcomes. For insomnia, an odds ratio (OR) of 1.24, 95% CI 1.03-1.51 was observed in the highest decile of mobile phone call-time (>258 min/week). With weights assigned to call-time to account for the lower RF-EMF exposure from Universal Mobile Telecommunications Service (UMTS, 3G) than from Global System for Mobile Communications (GSM, 2G) the OR was 1.09 (95% CI 0.89-1.33) in the highest call-time decile. CONCLUSION: Insomnia was slightly more common among mobile phone users in the highest call-time category, but adjustment for the considerably lower RF-EMF exposure from the UMTS than the GSM network suggests that this association is likely due to other factors associated with mobile phone use than RF-EMF. No association was observed for other sleep outcomes. In conclusion, findings from this study do not support the hypothesis that RF-EMF from mobile phone use has long-term effects on sleep quality.
Mustafa R, Mens M, Pinto RJ, et al., 2020, Metabolomic signatures of microRNAs in cardiovascular traits: A Mendelian randomization analysis, Annual Meeting of the International-Genetic-Epidemiology-Society, Publisher: WILEY, Pages: 506-506, ISSN: 0741-0395
Robinson O, Chadeau Hyam M, Karaman I, et al., 2020, Determinants of accelerated metabolomic and epigenetic ageing in a UK cohort, Aging Cell, Vol: 19, Pages: 1-13, ISSN: 1474-9718
Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography–mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.
Graham NSN, Junghans C, Downes R, et al., 2020, SARS-CoV-2 infection, clinical features and outcome of COVID-19 in United Kingdom nursing homes
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>To understand SARS-Co-V-2 infection and transmission in UK nursing homes in order to develop preventive strategies for protecting the frail elderly residents.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>An outbreak investigation.</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>4 nursing homes affected by COVID-19 outbreaks in central London.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>394 residents and 70 staff in nursing homes.</jats:p></jats:sec><jats:sec><jats:title>Interventions</jats:title><jats:p>Two point-prevalence surveys one week apart where residents underwent SARS-CoV-2 testing and had relevant symptoms documented. Asymptomatic staff from three of the four homes were also offered SARS-CoV-2 testing.</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>All-cause mortality, and mortality attributed to COVID-19 on death certificates. Prevalence of SARS-CoV-2 infection and symptoms in residents and staff.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Overall, 26% (95% confidence interval 22 to 31) of residents died over the two-month period. All-cause mortality increased by 203% (95% CI 70 to 336). Systematic testing identified 40% (95% CI 35 to 46) of residents, of whom 43% (95% CI 34 to 52) were asymptomatic and 18% (95% CI 11 to 24) had atypical symptoms, as well as 4% (95% CI -1 to 9) of asymptomatic staff who tested positive for SARS-CoV-2.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The SARS-CoV-2 outbreak was associated with a ver
de las Fuentes L, Sung YJ, Noordam R, et al., 2020, Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci, Molecular Psychiatry, Vol: 26, Pages: 2111-2125, ISSN: 1359-4184
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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