Publications
198 results found
Chadeau-Hyam M, Wang H, Eales O, et al., 2021, REACT-1 study round 14: High and increasing prevalence of SARS-CoV-2 infection among school-aged children during September 2021 and vaccine effectiveness against infection in England
Background: England experienced a third wave of the COVID-19 epidemic from end May2021 coinciding with the rapid spread of Delta variant. Since then, the population eligible forvaccination against COVID-19 has been extended to include all 12-15-year-olds, and abooster programme has been initiated among adults aged 50 years and over, health careand care home workers, and immunocompromised people. Meanwhile, schoolchildren havereturned to school often with few COVID-19-related precautions in place.Methods: In the REal-time Assessment of Community Transmission-1 (REACT-1) study,throat and nose swabs were sent to non-overlapping random samples of the populationaged 5 years and over in England. We analysed prevalence of SARS-CoV-2 using reversetranscription-polymerase chain reaction (RT-PCR) swab-positivity data from REACT-1 round14 (between 9 and 27 September 2021). We combined results for round 14 with round 13(between 24 June and 12 July 2021) and estimated vaccine effectiveness and prevalence ofswab-positivity among double-vaccinated individuals. Unlike all previous rounds, in round 14,we switched from dry swabs transported by courier on a cold chain to wet swabs usingsaline. Also, at random, 50% of swabs (not chilled until they reached the depot) weretransported by courier and 50% were sent through the priority COVID-19 postal service.Results: We observed stable or rising prevalence (with an R of 1.03 (0.94, 1.14) overall)during round 14 with a weighted prevalence of 0.83% (0.76%, 0.89%). The highest weightedprevalence was found in children aged 5 to 12 years at 2.32% (1.96%, 2.73%) and 13 to 17years at 2.55% (2.11%, 3.08%). All positive virus samples analysed correspond to the Deltavariant or sub-lineages of Delta with one instance of the E484K escape mutation detected.The epidemic was growing in those aged 17 years and under with an R of 1.18 (1.03, 1.34),but decreasing in those aged 18 to 54 years with an R of 0.81 (0.68, 0.97). For allparticipants and all vaccin
Bowden S, Bodinier B, Paraskevaidi M, et al., 2021, 200 Can methylation signals of cervical cancer enhance cervical screening?: an epigenome-wide association study on the Illumina 850k array, ESGO 2021 Congress, Publisher: BMJ Publishing Group, Pages: A12-A17, ISSN: 1048-891X
Misra N, Bastien P, Bourokba N, et al., 2021, Metabolomics, a tool to construe skin phenotype, Publisher: ELSEVIER SCIENCE INC, Pages: S162-S162, ISSN: 0022-202X
Elliott J, Whitaker M, Bodinier B, et al., 2021, Predictive symptoms for COVID-19 in the community: REACT-1 study of over one million people, PLoS Medicine, Vol: 18, Pages: 1-14, ISSN: 1549-1277
Background:Rapid detection, isolation and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and whether predictive symptoms differ between B.1.1.7 (Alpha) lineage (predominating as of April 2021in the USA, UK and elsewhere) and wild type.Methods and Findings:We obtained throat and nose swabs with valid SARS-CoV-2 polymerase chain reaction (PCR) test results from 1,147,370 volunteers aged 5 years and above (6,450 positives) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least one symptom identified seven symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same seven symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. Main
Wielscher M, Mandaviya P, Kuehnel B, et al., 2021, DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases
<jats:title>Abstract</jats:title> <jats:p>We performed a trans-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We found 1,511 independent differentially methylated loci associated with CRP. These CpG sites showed correlation structures across chromosomes, and were primarily situated in euchromatin, depleted in CpG islands and enriched in transcription factor binding sites and genomic enhancer regions. Mendelian randomisation analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis revealed obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we found that a fully activated CpG signature, meaning that if all novel discovered CpGs would either be fully methylated or unmethylated depending on their CRP associated direction of effect, the risk of myocardial infarction would be increased by 20.3%, risk of T2D by 11.3% and the risk of COPD by 5.6%.</jats:p>
Vlaanderen J, de Hoogh K, Hoek G, et al., 2021, Developing the building blocks to elucidate the impact of the urban exposome on cardiometabolic-pulmonary disease: The EU EXPANSE project, Environmental Epidemiology, Vol: 5, ISSN: 2474-7882
By 2030, more than 80% of Europe's population will live in an urban environment. The urban exposome, consisting of factors such as where we live and work, where and what we eat, our social network, and what chemical and physical hazards we are exposed to, provides important targets to improve population health. The EXPANSE (EXposome Powered tools for healthy living in urbAN SEttings) project will study the impact of the urban exposome on the major contributors to Europe's burden of disease: Cardio-Metabolic and Pulmonary Disease. EXPANSE will address one of the most pertinent questions for urban planners, policy makers, and European citizens: "How to maximize one's health in a modern urban environment?" EXPANSE will take the next step in exposome research by (1) bringing together exposome and health data of more than 55 million adult Europeans and OMICS information for more than 2 million Europeans; (2) perform personalized exposome assessment for 5,000 individuals in five urban regions; (3) applying ultra-high-resolution mass-spectrometry to screen for chemicals in 10,000 blood samples; (4) evaluating the evolution of the exposome and health through the life course; and (5) evaluating the impact of changes in the urban exposome on the burden of cardiometabolic and pulmonary disease. EXPANSE will translate its insights and innovations into research and dissemination tools that will be openly accessible via the EXPANSE toolbox. By applying innovative ethics-by-design throughout the project, the social and ethical acceptability of these tools will be safeguarded. EXPANSE is part of the European Human Exposome Network.
Whitaker M, Elliott J, Chadeau-Hyam M, et al., 2021, Persistent symptoms following SARS-CoV-2 infection in a random community sample of 508,707 people
IntroductionLong COVID, describing the long-term sequelae after SARS-CoV-2 infection, remains a poorlydefined syndrome. There is uncertainty about its predisposing factors and the extent of theresultant public health burden, with estimates of prevalence and duration varying widely.MethodsWithin rounds 3–5 of the REACT-2 study, 508,707 people in the community in England wereasked about a prior history of COVID-19 and the presence and duration of 29 differentsymptoms. We used uni- and multivariable models to identify predictors of persistence ofsymptoms (12 weeks or more). We estimated the prevalence of symptom persistence at 12weeks, and used unsupervised learning to cluster individuals by symptoms experienced.ResultsAmong the 508,707 participants, the weighted prevalence of self-reported COVID-19 was 19.2%(95% CI: 19.1,19.3). 37.7% of 76,155 symptomatic people post COVID-19 experienced at leastone symptom, while 14.8% experienced three or more symptoms, lasting 12 weeks or more. Thisgives a weighted population prevalence of persistent symptoms of 5.75% (5.68, 5.81) for one and2.22% (2.1, 2.26) for three or more symptoms. Almost a third of people 8,771/28,713 (30.5%)with at least one symptom lasting 12 weeks or more reported having had severe COVID-19symptoms (“significant effect on my daily life”) at the time of their illness, giving a weightedprevalence overall for this group of 1.72% (1.69,1.76). The prevalence of persistent symptomswas higher in women than men (OR: 1.51 [1.46,1.55]) and, conditional on reporting symptoms,risk of persistent symptoms increased linearly with age by 3.5 percentage points per decade oflife. Obesity, smoking or vaping, hospitalisation , and deprivation were also associated with ahigher probability of persistent symptoms, while Asian ethnicity was associated with a lowerprobability. Two stable clusters were identified based on symptoms that persisted for 12 weeks ormore: in the largest cluster, tiredness predominated
Elliott J, Whitaker M, Bodinier B, et al., 2021, Complementary Variable Selection Methods Highlight Joint Contribution Of Cystatin C And Apolipoprotein B For Cardiovascular Risk Prediction, Scientific Sessions of the American-Heart-Association on Epidemiological and Prevention (EPI)/Lifestyle and Cardiometabolic Health, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
Elliott J, Bodinier B, Whitaker M, et al., 2021, Cardiovascular Disease, Hypertension, Diabetes And Cystatin C Jointly Predict Covid-19 Mortality Alongside Age, Male Sex And Black Ethnicity, Scientific Sessions of the American-Heart-Association on Epidemiological and Prevention (EPI)/Lifestyle and Cardiometabolic Health, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0009-7322
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Tayal U, Fecht D, Chadeau-Hyam M, et al., 2021, Air pollution and adverse cardiac remodelling in patients with dilated cardiomyopathy, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: Elsevier, Pages: 600-600, ISSN: 0735-1097
Elliott J, Bodinier B, Whitaker M, et al., 2021, COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors, European Journal of Epidemiology, Vol: 36, Pages: 299-309, ISSN: 0393-2990
Background: Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK Biobank ohort, we investigate risk factors for COVID-19 mortality in comparison withnon-COVID-19mortality.MethodsWe investigated demographic, social (education, income, housing, employment), lifestyle (smoking, drinking, body mass index), biological (lipids, cystatin C, vitamin D), medical (comorbidities, medications) and environmental (air pollution) data from UK Biobank (N=473,550) in relation to 459 COVID-19 and 2,626 non-COVID-19 deaths to 21 September 2020. We used univariate, multivariable and penalised regression models. Results: Age (OR=2.76[2.18-3.49]per S.D. [8.1 years], p=2.6x10-17), male sex (OR=1.47[1.26-1.73], p=1.3x10-6) and Black versus White ethnicity (OR=1.21[1.12-1.29], p=3.0x10-7) were independently associated with and jointly explanatory of (area under receiver operating characteristic curve, AUC=0.79) increased risk of COVID-19 mortality. In multivariable regression, alongside demographic covariates, being a healthcare worker, current smoker, having cardiovascular disease, hypertension, diabetes, autoimmune disease, and oral steroid use at enrolment were independently associated with COVID-19 mortality. Penalised regression models selected income, cardiovascular disease, hypertension, diabetes, cystatin C, and oral steroid use as jointly contributing to COVID-19 mortality risk; Black ethnicity, hypertension and oral steroid use contributed to COVID-19 but not non-COVID-19 mortality. Conclusions: Age, male sex and Black ethnicity, as well as comorbidities and oral steroid use at enrolment were associated with increased risk of COVID-19 death. Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants
Dagnino S, Bodinier B, Guida F, et al., 2021, Prospective identification of elevated circulating CDCP1 in patients years before onset of lung cancer, Cancer Research, Vol: 81, ISSN: 0008-5472
Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. In order to identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 pre-diagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared to controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer-related dysregulation of CDCP1 expression years before diagnosis.
Elliott J, Whitaker M, Bodinier B, et al., 2021, Symptom reporting in over 1 million people: community detection of COVID-19
Control of the SARS-CoV-2 epidemic requires rapid identification and isolation of infectedindividuals and their contacts. Community testing in England (Pillar 2) by polymerase chainreaction (PCR) is reserved for those reporting at least one of four ‘classic’ COVID-19 symptoms(loss or change of sense of smell, loss or change of sense of taste, fever, new continuous cough). 1Detection of positive cases in the community might be improved by including additionalsymptoms and their combinations. We used data from the REal-time Assessment of CommunityTransmission-1 (REACT-1) study to investigate symptom profiles for PCR positivity at differentages. Among rounds 2–7 (June to December 2020), an age-stratified, variable selection approachstably selected chills (all ages), headache (5–17 years), appetite loss (18–54 and 55+ years) andmuscle aches (18–54 years) as jointly and positively predictive of PCR positivity together withthe classic four symptoms. Between round 7 (November to December 2020) and round 8(January 2021) when new variant B.1.1.7 predominated, only loss or change of sense of smell(more predictive in round 7) and (borderline) new persistent cough (more predictive in round 8)differed between cases. At any level of PCR testing, triage based on the symptoms identifiedhere would result in more cases detected than the current approach .
Carmeli C, Kutalik Z, Mishra PP, et al., 2021, Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies, Scientific Reports, Vol: 11, ISSN: 2045-2322
Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
Chadeau M, Bodinier B, Vermeulen R, et al., 2020, Education, biological ageing, all-cause and cause-specific mortality and morbidity: UK Biobank Cohort Study, EClinicalMedicine, Vol: 29-30, ISSN: 2589-5370
BackgroundSocioeconomic position as measured by education may be embodied and affect the functioning of key physiological systems. Links between social disadvantage, its biological imprint, and cause-specific mortality and morbidity have not been investigated in large populations, and yet may point towards areas for public health interventions beyond targeting individual behaviours.MethodsUsing data from 366,748 UK Biobank participants with 13 biomarker measurements, we calculated a Biological Health Score (BHS, ranging from 0 to 1) capturing the level of functioning of five physiological systems. Associations between BHS and incidence of cardiovascular disease (CVD) and cancer, and mortality from all, CVD, cancer, and external causes were examined. We explored the role of education in these associations. Mendelian randomisation using genetic evidence was used to triangulate these findings.FindingsAn increase in BHS of 0.1 was associated with all-cause (HR = 1.14 [1.12–1.16] and 1.09 [1.07–1.12] in men and women respectively), cancer (HR = 1.11 [1.09–1.14] and 1.07 [1.04–1.10]) and CVD (HR = 1.25 [1.20–1.31] and 1.21 [1.11–1.31]) mortality, CVD incidence (HR = 1.15 [1.13–1.16] and 1.17 [1.15–1.19]). These associations survived adjustment for education, lifestyle-behaviours, body mass index (BMI), co-morbidities and medical treatments. Mendelian randomisation further supported the link between the BHS and CVD incidence (HR = 1.31 [1.21–1.42]). The BHS contributed to CVD incidence prediction (age-adjusted C-statistic = 0.58), other than through education and health behaviours.InterpretationThe BHS captures features of the embodiment of education, health behaviours, and more proximal unknown factors which all complementarily contribute to all-cause, cancer and CVD morbidity and premature death.
Laine JE, Bodinier B, Robinson O, et al., 2020, Prenatal exposure to multiple air pollutants, mediating molecular mechanisms, and shifts in birthweight., Environmental Science and Technology (Washington), Vol: 54, Pages: 14502-14513, ISSN: 0013-936X
Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NO x , ultrafine particles (UFP), and oxidative potential (OP) of PM2.5 on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to -0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2 were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.
Maurel M, Castagné R, Berger E, et al., 2020, Patterning of educational attainment across inflammatory markers: Findings from a multi-cohort study, Brain, Behavior, and Immunity, Vol: 90, Pages: 303-310, ISSN: 0889-1591
BACKGROUND: Evidence suggests that the inflammatory reaction, an adaptive response triggered by a variety of harmful stimuli and conditions involved in the risk and development of many chronic diseases, is a potential pathway through which the socioeconomic environment is biologically embedded. Difficulty in interpreting the role of the inflammatory system in the embodiment dynamic arises because of heterogeneity across studies that use a limited but varied number of inflammatory markers. There is no consensus in the literature as to which inflammatory markers beyond the C-reactive protein and to a lesser extent interleukin 6 are related to the social environment. Accordingly, we aimed to investigate the association between educational attainment, and several markers of inflammation - C-reactive protein, fibrinogen, interleukin 6, interleukin 1β and tumor necrosis factor α- in 6 European cohort studies. METHODS: Up to 17,470 participants from six European cohort studies with data on educational attainment, health behaviors and lifestyle factors, and at least two different inflammatory markers. Four sub-datasets were drawn with varying numbers of participants to allow pairwise comparison of the social patterning of C-reactive protein and any other inflammatory markers. To evaluate within each sub-dataset the importance of the context and cohort specificities, linear regression-based analyses were performed separately for each cohort and combined in a random effect meta-analysis to determine the relationship between educational attainment and inflammation. RESULTS: We found that the magnitude of the relationship between educational attainment and five inflammatory biomarkers (C-reactive protein, fibrinogen, interleukin 6 and 1β and tumor necrosis factor α) was variable. By far the most socially patterned biomarker was C-reactive protein, followed by fibrinogen and to lesser extent interleukin 6, where a low educational attainment was associated w
Sanikini H, Muller DC, Chadeau-Hyam M, et al., 2020, Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort, PLoS One, Vol: 15, Pages: 1-22, ISSN: 1932-6203
BackgroundObesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort.MethodsAmong 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsBody mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65–3.28; HR = 1.56, 95%-CI:1.15–2.13; HR = 2.30, 95%-CI:1.47–3.57; HR = 1.71, 95%-CI:1.01–2.90; HR = 2.87, 95%-CI:1.88–4.38; HR = 1.96, 95%-CI:1.30–2.96; HR = 2.34, 95%-CI:1.70–3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00–3.37), waist circumference (HR = 2.21, 95%-CI:1.27–3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11–3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22–0.88) and last live birth (HR = 0.44, 95%-CI:0.22–0.87) were inversely associated with oesophageal squamous cell carc
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.
Vineis P, Chadeau M, Dagnino S, et al., 2020, What's new in the Exposome?, Environment International, Vol: 143, Pages: 1-13, ISSN: 0160-4120
The exposome concept refers to the totality of exposures from a variety of external and internal sources including chemical agents, biological agents, or radiation, from conception onward, over a complete lifetime. It encompasses also “psychosocial components” including the impact of social relations and socio-economic position on health. In this review we provide examples of recent contributions from exposome research, where we believe their application will be of the greatest value for moving forward. So far, environmental epidemiology has mainly focused on hard outcomes, such as mortality, disease exacerbation and hospitalizations. However, there are many subtle outcomes that can be related to environmental exposures, and investigations can be facilitated by an improved understanding of internal biomarkers of exposure and response, through the application of omic technologies. Second, though we have a wealth of studies on environmental pollutants, the assessment of causality is often difficult because of confounding, reverse causation and other uncertainties. Biomarkers and omic technologies may allow better causal attribution, for example using instrumental variables in triangulation, as we discuss here. Even more complex is the understanding of how social relationships (in particular socio-economic differences) influence health and imprint on the fundamental biology of the individual. The identification of molecular changes that are intermediate between social determinants and disease status is a way to fill the gap. Another field in which biomarkers and omics are relevant is the study of mixtures. Epidemiology often deals with complex mixtures (e.g. ambient air pollution, food, smoking) without fully disentangling the compositional complexity of the mixture, or with rudimentary approaches to reflect the overall effect of multiple exposures or components.From the point of view of disease mechanisms, most models hypothesize that several stages need t
Brewer H, Hirst Y, Sudha S, et al., 2020, Cancer Loyalty Card Study (CLOCS): protocol for an observational case-control study focusing on the patient interval in ovarian cancer diagnosis, BMJ Open, Vol: 10, Pages: 1-9, ISSN: 2044-6055
IntroductionOvarian Cancer is the eighth most common cancer in women worldwide, and about one infive women with ovarian cancer do not receive treatment, because they are too unwell by thetime they are diagnosed. Symptoms of ovarian cancer are non-specific or can be associatedwith other common conditions, and women experiencing these symptoms have been shownto self-manage them using over-the-counter medication. Results from a recent proof ofconcept study suggest there may be an increase in the purchases of pain killers andindigestion medication 10-12 months before ovarian cancer diagnosis. We propose a casecontrol study, as part of a larger project called the Cancer Loyalty Card Study (CLOCS), toinvestigate whether a significant change in medication purchases could be an indication forearly signs of ovarian cancer, using data already collected through store loyalty cards.Methods and AnalysisUsing a retrospective case-control design, we aim to recruit 500 women diagnosed withovarian cancer (cases) and 500 women without ovarian cancer (controls) in the UnitedKingdom who hold a loyalty card with at least one participating high street retailer. We willuse pre-existing loyalty card data to compare past purchase patterns of cases with those ofcontrols. In order to assess ovarian cancer risk in participants and their purchase patterns, wewill collect information from participants on ovarian cancer risk factors and clinical dataincluding symptoms experienced before diagnosis from recruited women with ovariancancer.Ethics and disseminationCLOCS was reviewed and approved by the North West - Greater Manchester South ResearchEthics Committee (19/NW/0427). Study outcomes will be disseminated through academicpublications, the study website, social media, and a report to the research sites that supportthe study once results are published.Study Registration NumbersCLOCS is registered with ISRCTN (14897082), NIHR portfolio (CPMS 43323), andclinicaltrials.gov (NCT03994653).
Petrovic D, Carmeli C, Bodinier B, et al., 2020, Exploring the relation between socioeconomic position and DNA methylation in a European population, Publisher: OXFORD UNIV PRESS, Pages: V385-V385, ISSN: 1101-1262
Chadeau M, Alfano R, Ghantous A, et al., 2020, A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism, Metabolism: clinical and experimental, Vol: 110, Pages: 1-12, ISSN: 0026-0495
BackgroundBirthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited.MethodsTo investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations.ResultsThis dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns.ConclusionsOur data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight.
Mancini FR, Laine JE, Tarallo S, et al., 2020, microRNA expression profiles and personal monitoring of exposure to particulate matter, Environmental Pollution, Vol: 263, ISSN: 0269-7491
An increasing number of findings from epidemiological studies support associations between exposure to air pollution and the onset of several diseases, including pulmonary, cardiovascular and neurodegenerative diseases, and malignancies. However, intermediate, and potentially mediating, biological mechanisms associated with exposure to air pollutants are largely unknown. Previous studies on the human exposome have shown that the expression of certain circulating microRNAs (miRNAs), regulators of gene expression, are altered upon exposure to traffic-related air pollutants. In the present study, we investigated the relationship between particulate matter (PM) smaller than 2.5 μm (PM2.5), PM2.5 absorbance (as a proxy of black carbon and soot), and ultrafine-particles (UFP, smaller than 0.1 μm), measured in healthy volunteers by 24 h personal monitoring (PEM) sessions and global expression levels of peripheral blood miRNAs. The PEM sessions were conducted in four European countries, namely Switzerland (Basel), United Kingdom (Norwich), Italy (Turin), and The Netherlands (Utrecht). miRNAs expression levels were analysed using microarray technology on blood samples from 143 participants. Seven miRNAs, hsa-miR-24-3p, hsa-miR-4454, hsa-miR-4763-3p, hsa-miR-425-5p, hsa-let-7d-5p, hsa-miR-502-5p, and hsa-miR-505-3p were significantly (FDR corrected) expressed in association with PM2.5 personal exposure, while no significant association was found between miRNA expression and the other pollutants. The results obtained from this investigation suggest that personal exposure to PM2.5 is associated with miRNA expression levels, showing the potential for these circulating miRNAs as novel biomarkers for air pollution health risk assessment.
Chadeau M, Castagne R, Kelly-Irving M, et al., 2020, A multi-omics approach to investigate the inflammatory response to life course socioeconomic position, Epigenomics, Vol: 12, ISSN: 1750-1911
Aims: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & Methods: We analysed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 EPIC-Italy participants. Results & Conclusions: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis-acting regulatory methylation sites (eMS) individually and jointly using several scores. Less advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.
Chadeau M, Petrovic D, Haba-Rubio J, et al., 2020, The contribution of sleep to social inequalities in cardiovascular disorders: a multi-cohort study, Cardiovascular Research, Vol: 116, Pages: 1514-1524, ISSN: 0008-6363
Aims: Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigate the role of sleep duration in the association between life-course socioeconomic status (SES) and CVD. Methods and Results We used cross-sectional data from eight European cohorts, totaling 111,205 participants. Life- course SES was assessed using father’s and adult occupational position. Self-reported sleep duration was categorized into recommended (6h-8.5h/night), long (>8.5h/night), and short (<6h/night). We examined two cardiovascular outcomes: coronary heart disease (CHD) and stroke. Main analyses were conducted using pooled data and examined the association between life-course SES and CVD, and the contribution of sleep duration to this gradient using counterfactual mediation. Low father’s occupational position was associated with an increased risk of CHD (men: OR=1.19, 95% CI [1.04;1.37]; women: OR=1.25, 95% CI 61 [1.02;1.54]), with marginal decrease of the gradient after accounting for adult occupational position (men: OR=1.17, 95% CI [1.02;1.35]; women: OR=1.22, 95% CI [0.99;1.52]), and no mediating effect by short sleep duration. Low adult occupational position was associated with an increased risk of CHD in both men and women (men: OR=1.48, 95% CI [1.14;1.92]; women: OR=1.53, 95% CI [1.04;2.21. Short sleep duration meaningfully contributed to the association between adult occupational position and CHD in men, with 13.4% mediation. Stroke did not exhibit a social patterning with any of the variables examined. Conclusion: This study suggests that inadequate sleep accounts to a meaningful proportion of the association between adult occupational position and coronary heart disease, at least in men. With slee
Tayal U, Fecht D, Chadeau M, et al., 2020, RESIDENTIAL EXPOSURE TO FINE PARTICULATE MATTER AIR POLLUTION IS ASSOCIATED WITH IMPAIRED CARDIAC PHENOTYPES IN DILATED CARDIOMYOPATHY, Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 1355-6037
Appenzeller BMR, Chadeau-Hyam M, Aguilar L, 2020, Skin exposome science in practice : current evidence on hair biomonitoring and future perspectives, JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, Vol: 34, Pages: 26-30, ISSN: 0926-9959
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Dagnino S, Bodinier B, Grigoryan H, et al., 2020, Agnostic Cys34-albumin adductomics and DNA methylation: implication of Nacetylcysteine in lung carcinogenesis years before diagnosis, International Journal of Cancer, Vol: 146, Pages: 3294-3303, ISSN: 0020-7136
Although smoking and oxidative stress are known contributors to lung carcinogenesis, theirmechanisms of action remain poorly understood. To shed light into these mechanisms, weapplied a novel approach using Cys34-adductomics in a lung cancer nested case-controlstudy (n=212). Adductomics profiles were integrated with DNA-methylation data atestablished smoking-related CpG sites measured in the same individuals. Our analysisidentified 42 Cys34-albumin adducts, of which 2 were significantly differentially abundant incases and controls: adduct of N-acetylcysteine (NAC, p=4.15x10-3) and of Cysteinyl-Glycine(Cys-Gly, p=7.89x10-3). Blood levels of the former were found associated to the methylationlevels at 11 smoking related CpG sites. We detect, for the first time in prospective bloodsamples, and irrespective of time-to-diagnosis, decreased levels of NAC adduct in lungcancer cases. Altogether, our results highlight the potential role of these adducts in theoxidative stress response contributing to lung carcinogenesis years before diagnosis.
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.
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