Imperial College London

Dr Marc Chadeau-Hyam

Faculty of MedicineSchool of Public Health

Reader in Computational Epidemiology & Exposome Science
 
 
 
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Contact

 

+44 (0)20 7594 1637m.chadeau

 
 
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Location

 

520Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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104 results found

Sanikini H, Muller DC, Sophiea M, Rinaldi S, Agudo A, Duell EJ, Weiderpass E, Overvad K, Tjønneland A, Halkjaer J, Boutron-Ruault M-C, Carbonnel F, Cervenka I, Boeing H, Kaaks R, Kühn T, Trichopoulou A, Martimianaki G, Karakatsani A, Pala V, Palli D, Mattiello A, Tumino R, Sacerdote C, Skeie G, Rylander C, López MDC, Sánchez M-J, Ardanaz E, Regnér S, Stocks T, Bueno-de-Mesquita B, Vermeulen RCH, Aune D, Tong TYN, Kliemann N, Murphy N, Chadeau-Hyam M, Gunter MJ, Cross AJet al., 2020, Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, International Journal of Cancer, Vol: 146, Pages: 929-942, ISSN: 0020-7136

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Journal article

Preston GW, Dagnino S, Ponzi E, Sozeri O, van Veldhoven K, Barratt B, Liu S, Grigoryan H, Lu SS, Rappaport SM, Chung KF, Cullinan P, Sinharay R, Kelly FJ, Chadeau-Hyam M, Vineis P, Phillips DHet al., 2020, Relationships between airborne pollutants, serum albumin adducts and short-term health outcomes in an experimental crossover study, Chemosphere, Vol: 239, ISSN: 0045-6535

Exposure to air pollution can have both short-term and long-term effects on health. However, the relationships between specific pollutants and their effects can be obscured by characteristics of both the pollution and the exposed population. One way of elucidating the relationships is to link exposures and internal changes at the level of the individual. To this end, we combined personal exposure monitoring (59 individuals, Oxford Street II crossover study) with mass-spectrometry-based analyses of putative serum albumin adducts (fixed-step selected reaction monitoring). We attempted to infer adducts' identities using data from another, higher-resolution mass spectrometry method, and were able to detect a semi-synthetic standard with both methods. A generalised least squares regression method was used to test for associations between amounts of adducts and pollution measures (ambient concentrations of nitrogen dioxide and particulate matter), and between amounts of adducts and short-term health outcomes (measures of lung health and arterial stiffness). Amounts of some putative adducts (e.g., one with a positive mass shift of ∼143 Da) were associated with exposure to pollution (11 associations), and amounts of other adducts were associated with health outcomes (eight associations). Adducts did not appear to provide a link between exposures and short-term health outcomes.

Journal article

Laine J, Baltar VT, Stringini S, Gandini M, Chadeau-Hyam M, Kivimaki M, Severi G, Perduca V, Hodge AM, Dugué P-A, Giles GG, Milne RL, Barros H, Sacerdote C, Krogh V, Panico S, Tumino R, Goldberg M, Marie Z, Cyrille D, Vineis Pet al., Reducing socioeconomic inequalities in all-cause mortality: a counterfactual mediation approach, International Journal of Epidemiology, ISSN: 0300-5771

Background: Socioeconomicinequalities inmortality arewell established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear.We evaluated the role of multiple modifiable intermediate risk factors underlyingsocioeconomicassociated-mortality and quantifiedthe potentialimpact of reducing early all-cause mortality by hypothetically altering socioeconomic risk factors. Methods: Data were fromsevencohort studies participating in the LIFEPATH consortium (total n=179,090). Using bothsocioeconomic position (SEP) (based on occupation) and education, we estimated thenaturaldirect effect on all-cause mortality, and thenatural indirect effect via the joint mediatingrole of smoking, alcohol intake, dietary patterns, physical activity, body mass index,hypertension, diabetes, and coronary artery disease.Hazard ratios(HR)were estimated, using counterfactual natural effect modelsunder different hypothetical actions of either lower or higher SEP or education. Results: Lower SEP and educationwereassociated with anincreaseinall-cause mortalitywithin an average follow up time of 17.5 years.Mortality wasreducedviamodelled hypothetical actions of increasing SEP oreducation. Through higher educationtheHR was0.85(95% confidence interval (CI) 0.84, 0.86) for women and 0.71(95% CI 0.70, 0.74)for men,compared to lower education. In addition, 34% and 38% of the effect was jointlymediatedfor womenand men, respectively. The benefits from alteringSEP were slightly more modest.Conclusions: Theseobservational findings supportpoliciesto reducemortalityboththrough improving socioeconomic circumstances and increasing education,andby altering intermediaries, such as lifestyle behaviours and morbidities.

Journal article

Bowden SJ, Kalliala I, Veroniki AA, Arbyn M, Mitra A, Lathouras K, Mirabello L, Chadeau-Hyam M, Paraskevaidis E, Flanagan JM, Kyrgiou Met al., 2019, The use of Human Papillomavirus DNA Methylation in cervical intraepithelial neoplasia: a systematic review and meta-analysis, EBioMedicine, Vol: 50, Pages: 246-259, ISSN: 2352-3964

BackgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus(HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detectinghigh-grade cervical intra-epithelial neoplasia (CIN).MethodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted induplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effectsbinary regression model were applied to determine pooled effect estimates.Findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamousintra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN(≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled differencein mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3%(95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse(pooled sensitivity 77% (95%CI:63–87), specificity 64% (95%CI:55–71), area under the curve (0·73(95%CI:0·69–0·77)).InterpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use islimited by the need for a multi-genotype and standardised ass

Journal article

Chadeau M, Petrovic D, Haba-Rubio J, de Mestral Vargas C, Kelly-Irving M, Vineis P, Kivimaki M, Nyberg S, Gandini M, Bochud M, Vollenweider P, dErrico A, Barros H, Fraga S, Goldberg M, Zins M, Steptoe A, Delpierre C, Heinzer R, Carmeli C, Stringhini Set al., The contribution of sleep to social inequalities in cardiovascular disorders: a multi-cohort study, Cardiovascular Research, 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

Journal article

Chadeau-Hyam M, Karimi M, Castagne R, Bodinier B, Delpierre C, Kelly-Irving Met al., 2019, A socially patterned Biological Health Score and mortality in Understanding Society and UKBiobank, Publisher: OXFORD UNIV PRESS, Pages: 89-89, ISSN: 1101-1262

Conference paper

Castagne R, Chadeau-Hyam M, Karimi M, Stringhini S, Vineis P, Delpierre C, Kelly-Irving Met al., 2019, Social patterning of inflammation over the lifecourse and its relationship with mortality, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262

Conference paper

Carmeli C, Kutalik Z, Kelly-Irving M, Delpierre C, Bochud M, Kivimaki M, Vineis P, Chadeau-Hyam M, Dermitzakis E, Stringhini Set al., 2019, Early life socioeconomic position and adult systemic inflammation: the role of gene regulation, Publisher: OXFORD UNIV PRESS, Pages: 88-88, ISSN: 1101-1262

Conference paper

Chadeau M, Dagnino S, Bodinier B, Grigoryan H, Rappaport S, Karimi M, Guida F, Polidoro S, Edmands W, Naccarati A, Sacerdote C, Krogh V, Vermeulen R, Vineis Pet al., Agnostic Cys34-albumin adductomics and DNA methylation: implication of Nacetylcysteine in lung carcinogenesis years before diagnosis, International Journal of Cancer, 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.

Journal article

Krauskopf J, van Veldhoven K, Chadeau-Hyam M, Vermeulen R, Carrasco-Turigas G, Nieuwenhuijsen M, Vineis P, de Kok TM, Kleinjans JCSet al., 2019, Cell-free, circulating microRNAs reflect air pollution-induced environmental health risks, 55th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology - Science Providing Solutions, Publisher: ELSEVIER IRELAND LTD, Pages: S68-S68, ISSN: 0378-4274

Conference paper

Tzoulaki I, Castagné R, Boulangé CL, Karaman I, Chekmeneva E, Evangelou E, Ebbels TMD, Kaluarachchi MR, Chadeau-Hyam M, Mosen D, Dehghan A, Moayyeri A, Ferreira DLS, Guo X, Rotter JI, Taylor KD, Kavousi M, De Vries PS, Lehne B, Loh M, Hofman A, Nicholson JK, Chambers J, Gieger C, Holmes E, Tracy R, Kooner J, Greenland P, Franco OH, Herrington D, Lindon JC, Elliott Pet al., 2019, Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease, European Heart Journal, Vol: 40, Pages: 2883-2896, ISSN: 1522-9645

Aims: To characterise serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and Results: We used untargeted one-dimensional (1D) serum metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3,569 participants from the Rotterdam and LOLIPOP Studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 NMR measured metabolites were associated with CAC and/or IMT, P =1.3x10-14 to 6.5x10-6 (discovery), P =4.2x10-14 to 4.4x10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched-chain and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide and lactate as well as apolipoprotein B (P <0.05). Conclusion: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclero

Journal article

Castagne R, Kelly-Irving M, Kyrtopoulos SA, Vineis P, Chadeau-Hyam M, Delpierre Cet al., 2019, A MULTI-OMICS APPROACH TO INVESTIGATE THE INFLAMMATORY RESPONSE OF LIFE COURSE SOCIOECONOMIC POSITION: FINDINGS FROM EPIC-ITALY, Publisher: BMJ PUBLISHING GROUP, Pages: A40-A40, ISSN: 0143-005X

Conference paper

Karimi M, Castagne R, Delpierre C, Albertus G, Berger E, Vineis P, Kumari M, Kelly-Irving M, Chadeau Met al., 2019, Early-life inequalities and biological ageing: A multi-system biological health score approach in the Understanding Society study, Journal of Epidemiology and Community Health, Vol: 73, Pages: 693-702, ISSN: 0143-005X

Social position is known to play a role in the quality of ageing, notably through the stimulation/dysregulation of key physiological systems in response to external stresses. Using data from one wave of the Understanding Society panel study including 9,088 participants, we defined, as an extension of the Allostatic Load, a synthetic biological health score (BHS) capturing the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular, and metabolic systems), and two organs (liver and kidney). We used 16 established blood-derived biomarkers of these systems to calculate the BHS and explored the relative contribution of socio-economic position to the BHS and its main components across age groups.We identified a systematic decreasing education-related gradient of the BHS (p<0.001) leading to lower biological risk in participants with longer education. Education-related differences in the BHS were detected early in life, and were not attributable to lifestyle and behavioural factors. We found a consistent contribution of the inflammatory and metabolic systems to the overall score throughout from early adulthood onwards, while the contribution of the other four systems seem to vary across age groups and gender. Our findings highlight the social-to-biological processes ultimately leading to health inequalities, and suggest that such disparities can already be detected in the 20-40 years old age group and cannot be fully explained by lifestyle and behavioural factors. This may define early adulthood social condition as a precursor to accelerated biological ageing and as an important target for public health policies.

Journal article

Krauskopf J, van Veldhoven K, Chadeau-Hyam M, Vermeulen R, Carrasco-Turigas G, Nieuwenhuijsen M, Vineis P, de Kok TM, Kleinjans JCet al., 2019, Short-term exposure to traffic-related air pollution reveals a compound-specific circulating miRNA profile indicating multiple disease risks, Environment International, Vol: 128, Pages: 193-200, ISSN: 0160-4120

Traffic-related air pollution (TRAP) is a complex mixture of compounds that contributes to the pathogenesis of many diseases including several types of cancer, pulmonary, cardiovascular and neurodegenerative diseases, and more recently also diabetes mellitus. In search of an early diagnostic biomarker for improved environmental health risk assessment, recent human studies have shown that certain extracellular miRNAs are altered upon exposure to TRAP. Here, we present a global circulating miRNA analysis in a human population exposed to different levels of TRAP. The cross-over study, with sampling taking place during resting and physical activity in two different exposure scenarios, included for each subject personal exposure measurements of PM10,PM2.5, NO, NO2, CO, CO2, BC and UFP. Next-generation sequencing technology was used to identify global circulating miRNA levels across all subjects. We identified 8 miRNAs to be associated with the mixture of TRAP and 27 miRNAs that were associated with the individual pollutants NO, NO2, CO, CO2, BC and UFP. We did not find significant associations between miRNA levels and PM10 or PM2.5. Integrated network analysis revealed that these circulating miRNAs are potentially involved in processes that are implicated in the development of air pollution-induced diseases. Altogether, this study demonstrates that signatures consisting of circulating miRNAs present a potential novel biomarker to be used in health risk assessment.

Journal article

McCrory C, Leahy S, Ribeiro AI, Fraga S, Barros H, Avendano M, Vineis P, Layte R, Alenius H, Baglietto L, Bartley M, Bellone M, Berger E, Bochud M, Candiani G, Carmeli C, Carra L, Castagne R, Chadeau-Hyam M, Cima S, Costa G, Courtin E, Delpierre C, D'Errico A, Donkin A, Dugue P-A, Elliott P, Fagherazzi G, Fiorito G, Gandini M, Gares V, Gerbouin-Rerrolle P, Giles G, Goldberg M, Greco D, Guida F, Hodge A, Karimi M, Karisola P, Kelly M, Kivimaki M, Laine J, Lang T, Laurent A, Lepage B, Lorsch D, Machell G, Mackenbach J, Marmot M, Milne R, Muennig P, Nusselder W, Petrovic D, Polidoro S, Preisig M, Recalcati P, Reinhard E, Ribeiro AI, Ricceri F, Robinson O, Valverde JR, Severi G, Simmons T, Stringhini S, Terhi V, Than J, Vergnaud A-C, Vigna-Taglianti F, Vollenweider P, Zins Met al., 2019, Maternal educational inequalities in measured body mass index trajectories in three European countries, PAEDIATRIC AND PERINATAL EPIDEMIOLOGY, Vol: 33, Pages: 226-237, ISSN: 0269-5022

Journal article

Fiorito G, McCrory C, Robinson O, Carmeli C, Rosales CO, Zhang Y, Colicino E, Dugué P-A, Artaud F, McKay GJ, Jeong A, Mishra PP, Nøst TH, Krogh V, Panico S, Sacerdote C, Tumino R, Palli D, Matullo G, Guarrera S, Gandini M, Bochud M, Dermitzakis E, Muka T, Schwartz J, Vokonas PS, Just A, Hodge AM, Giles GG, Southey MC, Hurme MA, Young I, McKnight AJ, Kunze S, Waldenberger M, Peters A, Schwettmann L, Lund E, Baccarelli A, Milne RL, Kenny RA, Elbaz A, Brenner H, Kee F, Voortman T, Probst-Hensch N, Lehtimäki T, Elliot P, Stringhini S, Vineis P, Polidoro S, BIOS Consortium, Lifepath consortiumet al., 2019, Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis, Aging, Vol: 11, Pages: 2045-2070, ISSN: 1945-4589

Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) hasbeen proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently,and themagnitude of the effectsdiffereddepending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception ofsmoking, which hada significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.

Journal article

Reimann B, Janssen BG, Alfano R, Ghantous A, Espin-Perez A, de Koko TM, Saenen ND, Cox B, Robinson O, Chadeau-Hyam M, Penders J, Herceg Z, Vineis P, Nawrot TS, Plusquin Met al., 2019, The cord blood insulin and mitochondrial DNA content related methylome, Frontiers in Genetics, Vol: 10, ISSN: 1664-8021

Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate

Journal article

Berger E, Castagne R, Chadeau M, Bochud M, d'Errico A, Gandini M, Karimi M, Kivimaki M, Krogh V, Marmot M, Panico S, Preisig M, Ricceri F, Sacerdote C, Steptoe A, Stringhini S, Tumino R, Vineis P, Delpierre C, Kelly-Irving Met al., 2019, Multi-cohort study identifies social determinants of systemic inflammation over the life course, Nature Communications, Vol: 10, ISSN: 2041-1723

Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.

Journal article

Chadeau M, van Veldhoven C, Kiss A, Keski-Rahkonen P, Robinot N, Scalbert A, Cullinan P, Chung KF, Collins P, Sinharay R, Barratt B, Nieuwenhuijsen M, Ambros Rodoreda A, Carrasco-Turigas G, Vlaanderen J, Vermeulen R, Kyrtopoulous S, Ponzi E, Vineis Pet al., 2019, Impact of short-term traffic-related air pollution on the metabolome – results from two metabolome-wide experimental studies, Environment International, Vol: 123, Pages: 124-131, ISSN: 0160-4120

Exposure to traffic-related air pollution (TRAP) has been associated with adverse health outcomes but underlying biological mechanisms remain poorly understood. Two randomized crossover trials were used here, the Oxford Street II (London) and the TAPAS II (Barcelona) studies, where volunteers were allocated to high or low air pollution exposures. The two locations represent different exposure scenarios, with Oxford Street characterized by diesel vehicles and Barcelona by normal mixed urban traffic. Levels of five and four pollutants were measured, respectively, using personal exposure monitoring devices. Serum samples were used for metabolomic profiling. The association between TRAP and levels of each metabolic feature was assessed. All pollutant levels were significantly higher at the high pollution sites. 29 and 77 metabolic features were associated with at least one pollutant in the Oxford Street II and TAPAS II studies, respectively, which related to 17 and 30 metabolic compounds. Little overlap was observed across pollutants for metabolic features, suggesting that different pollutants may affect levels of different metabolic features. After observing the annotated compounds, the main pathway suggested in Oxford Street II in association with NO2 was the acyl-carnitine pathway, previously found to be associated with cardio-respiratory disease. No overlap was found between the metabolic features identified in the two studies.

Journal article

Chadeau M, Alfano R, Guida F, Galobardes B, Delpierre C, Ghantous A, Henderson J, Herceg Z, Jain P, Nawrot T, Relton C, Vineis P, Castagne R, Plusquin Met al., 2019, Socioeconomic position during pregnancy and DNA methylation signatures at three stages across the early life: epigenome-wide association studies in the ALSPAC birth cohort, International Journal of Epidemiology, Vol: 48, ISSN: 1464-3685

BackgroundSocioeconomic experiences are recognized determinants of health, and recent work has shown that social disadvantages in early life may induce sustained biological changes at molecular level that are detectable later in life. However, the dynamics and persistence of biological embedding of socioeconomic position (SEP) remains vastly unexplored.MethodsUsing the data from the ALSPAC birth cohort, we performed epigenome-wide association studies of DNA methylation changes at three life stages (birth, n = 914; childhood at mean age 7.5 years, n = 973; and adolescence at mean age 15.5 years, n = 974), measured using the Illumina HumanMethylation450 Beadchip, in relation to pregnancy SEP indicators (maternal and paternal education and occupation).ResultsAcross the four early life SEP metrics investigated, only maternal education was associated with methylation levels at birth, and four CpGs mapped to SULF1, GLB1L2 and RPUSD1 genes were identified [false discovery rate (FDR)-corrected P-value <0.05]. No epigenetic signature was found associated with maternal education in child samples, but methylation levels at 20 CpG loci were found significantly associated with maternal education in adolescence. Although no overlap was found between the differentially methylated CpG sites at different ages, we identified two CpG sites at birth and during adolescence which are 219 bp apart in the SULF1 gene that encodes an heparan sulphatase involved in modulation of signalling pathways. Using data from an independent birth cohort, the ENVIRONAGE cohort, we were not able to replicate these findings.ConclusionsTaken together, our results suggest that parental SEP, and particularly maternal education, may influence the offspring’s methylome at birth and adolescence.

Journal article

Niedzwiecki MM, Walker DI, Vermeulen R, Chadeau-Hyam M, Jones DP, Miller GWet al., 2019, The exposome: molecules to populations, Annual Review of Pharmacology and Toxicology, Vol: 59, Pages: 6.1-6.21, ISSN: 0362-1642

Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale. These forces can also be assessed at systems and network levels, providing a framework for advances in pharmacology and toxicology. The exposome paradigm can improve the analysis of drug interactions and detection of adverse effects of drugs and toxicants and provide data on biological responses to exposures. The comprehensive model can provide data at the individual level for precision medicine, group level for clinical trials, and population level for public health. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Journal article

Espin-Perez A, Hebels DGAJ, Kiviranta H, Rantakokko P, Georgiadis P, Botsivali M, Bergdahl IA, Palli D, Spath F, Johansson A, Chadeau-Hyam M, Kyrtopoulos SA, Kleinjans JCS, de Kok TMCMet al., 2019, Identification of Sex-Specific Transcriptome Responses to Polychlorinated Biphenyls (PCBs), SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322

Journal article

Chadeau M, Campanella G, Gunter MJ, Polidoro S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Fiorito G, Guarrera S, Iacovello L, Bergdahl I, Melin B, Lenner P, de Kok T, Georgiadis P, Kleinjans J, Kyrtopoulos S, Bueno-de-Mesquita B, Lillycrop K, May A, Onland-Moret C, Murray R, Riboli E, Verschuren M, Lund E, Mode N, Sandanger TM, Fiano V, Trevisan M, Matullo G, Froguel P, Elliott P, Vineis Pet al., 2018, Epigenome-wide association study of adiposity and future risk of obesity-related diseases, International Journal of Obesity, Vol: 42, Pages: 2022-2035, ISSN: 0307-0565

BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associa

Journal article

Alfano R, Herceg Z, Nawrot TS, Chadeau-Hyam M, Ghantous A, Plusquin Met al., 2018, The impact of air pollution on our epigenome: how far is the evidence? (A systematic review), Current Environmental Health Reports, Vol: 5, Pages: 544-578, ISSN: 2196-5412

Purpose of ReviewThis systematic review evaluated existing evidence linking air pollution exposure in humans to major epigenetic mechanisms: DNA methylation, microRNAs, long noncoding RNAs, and chromatin regulation.Recent FindingsEighty-two manuscripts were eligible, most of which were observational (85%), conducted in adults (66%) and based on DNA methylation (79%).SummaryMost observational studies, except panel, demonstrated modest effects of air pollution on the methylome. Panel and experimental studies revealed a relatively large number of significant methylome alterations, though based on smaller sample sizes. Particulate matter levels were positively associated in several studies with global or LINE-1 hypomethylation, a hallmark of several diseases, and with decondensed chromatin structure. Several air pollution species altered the DNA methylation clock, inducing accelerated biological aging. The causal nature of identified associations is not clear, however, especially that most originate from countries with low air pollution levels. Existing evidence, gaps, and perspectives are highlighted herein.

Journal article

Takeuchi F, Akiyama M, Matoba N, Katsuya T, Nakatochi M, Tabara Y, Narita A, Saw W-Y, Moon S, Spracklen CN, Chai J-F, Kim Y-J, Zhang L, Wang C, Li H, Li H, Wu J-Y, Dorajoo R, Nierenberg JL, Wang YX, He J, Bennett DA, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Rakugi H, Nakashima E, Isono M, Shirota M, Hozawa A, Ichihara S, Matsubara T, Yamamoto K, Kohara K, Igase M, Han S, Gordon-Larsen P, Huang W, Lee NR, Adair LS, Hwang MY, Lee J, Chee ML, Sabanayagam C, Zhao W, Liu J, Reilly DF, Sun L, Huo S, Edwards TL, Long J, Chang L-C, Chen C-H, Yuan J-M, Koh W-P, Friedlander Y, Kelly TN, Wei WB, Xu L, Cai H, Xiang Y-B, Lin K, Clarke R, Walters RG, Millwood IY, Li L, Chambers JC, Kooner JS, Elliott P, van der Harst P, Chen Z, Sasaki M, Shu X-O, Jonas JB, He J, Heng C-K, Chen Y-T, Zheng W, Lin X, Teo Y-Y, Tai E-S, Cheng C-Y, Wong TY, Sim X, Mohlke KL, Yamamoto M, Kim B-J, Miki T, Nabika T, Yokota M, Kamatani Y, Kubo M, Kato Net al., 2018, Interethnic analyses of blood pressure loci in populations of East Asian and European descent., Nature Communications, Vol: 9, ISSN: 2041-1723

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Journal article

Sandanger T, Nost T, Guida F, Rylander C, Campanella G, Muller D, van Dongen J, Boomsma D, Johansson M, Vineis P, Vermeulen R, Lund E, Chadeau Met al., 2018, DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort, Scientific Reports, Vol: 8, ISSN: 2045-2322

The majority of lung cancer is caused by tobacco smoking, and lung cancer-relevant epigenetic markers have been identified in relation to smoking exposure. Still, smoking-related markers appear to mediate little of the effect of smoking on lung cancer. Thus in order to identify disease-relevant markers and enhance our understanding of pathways, a wide search is warranted. Through an epigenome-wide search within a case-control study (131 cases, 129 controls) nested in a Norwegian prospective cohort of women, we found 25 CpG sites associated with lung cancer. Twenty-three were classified as associated with smoking (LC-AwS), and two were classified as unassociated with smoking (LC-non-AwS), as they remained associated with lung cancer after stringent adjustment for smoking exposure using the comprehensive smoking index (CSI): cg10151248 (PC, CSI-adjusted odds ratio (OR) = 0.34 [0.23–0.52] per standard deviation change in methylation) and cg13482620 (B3GNTL1, CSI-adjusted OR = 0.33 [0.22–0.50]). Analysis among never smokers and a cohort of smoking-discordant twins confirmed the classification of the two LC-non-AwS CpG sites. Gene expression profiles demonstrated that the LC-AwS CpG sites had different enriched pathways than LC-non-AwS sites. In conclusion, using blood-derived DNA methylation and gene expression profiles from a prospective lung cancer case-control study in women, we identified 25 CpG lung cancer markers prior to diagnosis, two of which were LC-non-AwS markers and related to distinct pathways.

Journal article

Espín-Pérez A, Krauskopf J, Chadeau-Hyam M, van Veldhoven K, Chung F, Cullinan P, Piepers J, van Herwijnen M, Kubesch N, Carrasco-Turigas G, Nieuwenhuijsen M, Vineis P, Kleinjans JCS, de Kok TMCMet al., 2018, Short-term transcriptome and microRNAs responses to exposure to different air pollutants in two population studies, Environmental Pollution, Vol: 242, Pages: 182-190, ISSN: 0269-7491

Diesel vehicle emissions are the major source of genotoxic compounds in ambient air from urban areas. These pollutants are linked to risks of cardiovascular diseases, lung cancer, respiratory infections and adverse neurological effects. Biological events associated with exposure to some air pollutants are widely unknown but applying omics techniques may help to identify the molecular processes that link exposure to disease risk. Most data on health risks are related to long-term exposure, so the aim of this study is to investigate the impact of short-term exposure (two hours) to air pollutants on the blood transcriptome and microRNA expression levels. We analyzed transcriptomics and microRNA expression using microarray technology on blood samples from volunteers participating in studies in London, the Oxford Street cohort, and, in Barcelona, the TAPAS cohort. Personal exposure levels measurements of particulate matter (PM10, PM2.5), ultrafine particles (UFPC), nitrogen oxides (NO2, NO and NOx), black carbon (BC) and carbon oxides (CO and CO2) were registered for each volunteer. Associations between air pollutant levels and gene/microRNA expression were evaluated using multivariate normal models (MVN). MVN-models identified compound-specific expression of blood cell genes and microRNAs associated with air pollution despite the low exposure levels, the short exposure periods and the relatively small-sized cohorts. Hsa-miR-197-3p, hsa-miR-29a-3p, hsa-miR-15a-5p, hsa-miR-16-5p and hsa-miR-92a-3p are found significantly expressed in association with exposures. These microRNAs target also relevant transcripts, indicating their potential relevance in the research of omics-biomarkers responding to air pollution. Furthermore, these microRNAs are also known to be associated with diseases previously linked to air pollution exposure including several cancers such lung cancer and Alzheimer's disease. In conclusion, we identified in this study promising compound-specific mRN

Journal article

Mostafavi N, Vermeulen R, Ghantous A, Hoek G, Probst-Hensch N, Herceg Z, Tarallo S, Naccarati A, Kleinjans JCS, Imboden M, Jeong A, Morley D, Amaral AFS, van Nunen E, Gulliver J, Chadeau M, Vineis P, Vlaanderen Jet al., 2018, Acute changes in DNA methylation in relation to 24 h personal air pollution exposure measurements: a panel study in four European countries, Environment International, Vol: 120, Pages: 11-21, ISSN: 0160-4120

BackgroundOne of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites.ObjectiveWe investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes.MethodsWe collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM2.5), PM2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects.ResultsPersonal exposure to PM2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM2.5, 16 DMRs with ambient PM2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate.ConclusionThis study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation.

Journal article

Krauskopf J, Caiment F, van Veldhoven K, Chadeau-Hyam M, Sinharay R, Chung KF, Cullinan P, Collins P, Barratt B, Kelly FJ, Vermeulen R, de Kok TM, Kleinjans JCSet al., 2018, Short-term exposure to ambient motor vehicle emissions perturb the human circulating miRNA genome, 54th Congress of the European-Societies-of-Toxicology (EUROTOX) - Toxicology Out of the Box, Publisher: ELSEVIER IRELAND LTD, Pages: S85-S85, ISSN: 0378-4274

Conference paper

Vermeulen R, Saberi Hosnijeh F, Bodinier B, Portengen L, Liquet B, Garrido Manriquez J, Lokhorst H, Bergdahl I, Kyrtopoulos S, Johansson A-S, Georgiadis P, Melin B, Palli D, Krogh V, Panico S, Sacerdote C, Tumino R, Vineis P, Castagne RS, Chadeau Met al., 2018, Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma; univariate and functionally-informed multivariate analyses, International Journal of Cancer, Vol: 143, Pages: 1335-1347, ISSN: 0020-7136

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years prior to diagnosis (range, 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma) and matched controls. Linear mixed models, and Partial Least Square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes, and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed modelIrrespective of the model, our analyses identified associations linking blood lower immune markerslevels of and BCL incidence. In particular, we identified growth factors, and within that family, fibroblast growth factor-2 (FGF-2,p=7.2x10-4), ) and transforming growth factor alpha (TGF-α, p=6.5x10-5) and BCL incidence.Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p=7.8x10-7), TGF-α (p=4.08x10-5),fractalkine (p=1.12x10-3), monocyte chemotactic protein-3 (p=1.36x10-4), macrophage inflammatory protein 1-alpha (p=4.6x10-4), and vascular endothelial growth factor (p=4.23x10-5). , and vascular endothelial growth factor (VEGF), to be consistently (and inversely) associated with MM incidence. Our results also provided marginal support for already reported associations between chemokines and diffuse large B-Cell lymphoma (DLBCL), and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that GM-CSF levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression.In conclusion, our study suggests a role of gr

Journal article

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