Imperial College London

DrOliverRobinson

Faculty of MedicineSchool of Public Health

Lecturer in Molecular Epidemiology
 
 
 
//

Contact

 

o.robinson

 
 
//

Location

 

1103Building E - Sir Michael UrenWhite City Campus

//

Summary

 

Publications

Publication Type
Year
to

83 results found

Maitre L, Bustamante M, Hernández-Ferrer C, Thiel D, Lau C-HE, Siskos AP, Vives-Usano M, Ruiz-Arenas C, Pelegrí-Sisó D, Robinson O, Mason D, Wright J, Cadiou S, Slama R, Heude B, Casas M, Sunyer J, Papadopoulou EZ, Gutzkow KB, Andrusaityte S, Grazuleviciene R, Vafeiadi M, Chatzi L, Sakhi AK, Thomsen C, Tamayo I, Nieuwenhuijsen M, Urquiza J, Borràs E, Sabidó E, Quintela I, Carracedo Á, Estivill X, Coen M, González JR, Keun HC, Vrijheid Met al., 2022, Multi-omics signatures of the human early life exposome., Nat Commun, Vol: 13

Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1301 mother-child pairs, we associate individual exposomes consisting of >100 chemical, outdoor, social and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, proteins and metabolites) in childhood. We identify 1170 associations, 249 in pregnancy and 921 in childhood, which reveal potential biological responses and sources of exposure. Pregnancy exposures, including maternal smoking, cadmium and molybdenum, are predominantly associated with child DNA methylation changes. In contrast, childhood exposures are associated with features across all omics layers, most frequently the serum metabolome, revealing signatures for diet, toxic chemical compounds, essential trace elements, and weather conditions, among others. Our comprehensive and unique resource of all associations ( https://helixomics.isglobal.org/ ) will serve to guide future investigation into the biological imprints of the early life exposome.

Journal article

Robinson O, 2022, Characterization of the Degree of Food Processing in the European Prospective Investigation into Cancer and Nutrition: application of the Nova classification and validation using selected biomarkers of food processing, Frontiers in Nutrition, ISSN: 2296-861X

Journal article

Handakas E, Chang K, Khandpur N, Vamos EP, Millett C, Sassi F, Vineis P, Robinson Oet al., 2022, Metabolic profiles of ultra-processed food consumption and their role in obesity risk in British children, CLINICAL NUTRITION, Vol: 41, Pages: 2537-2548, ISSN: 0261-5614

Journal article

Freni Sterrantino A, Fiorito G, D'errico A, Virtanen M, Ala-Mursula L, Jarvelin M-R, Vineis P, Robinson Oet al., 2022, Association between work characteristics and epigenetic age acceleration: cross-sectional results from UK – Understanding Society study, Aging, Vol: 14, Pages: 7752-7773, ISSN: 1945-4589

Occupation-related stress and work characteristics are possible determinants of social inequalities in epigenetic aging but have been little investigated. Here, we investigate the association of several work characteristics with epigenetic age acceleration (AA) biomarkers.The study population included employed and unemployed men and women (n=631) from UK Understanding Society study. We evaluated the association of employment and work characteristics related to job type, job stability; job schedule; autonomy and influence at work; occupational physical activity; and feelings regarding the job with four epigenetic age acceleration biomarkers (Hannum, Horvath, PhenoAge, GrimAge) and pace of aging (DunedinPoAm, DunedinPACE). We fitted linear regression models, unadjusted and adjusted for established risk factors, and found the following associations for unemployment (years of acceleration): HorvathAA (1.51, 95%CI 0.08,2.95), GrimAgeAA (1.53, 95%CI 0.16,2.90) and 3.21 years for PhenoAA (95%CI 0.89,5.33). Job insecurity increased PhenoAA (1.83, 95%CI 0.003,3.67), while working at night was associated with an increase of 2.12 years in GrimAgeAA (95%CI 0.69,3.55). We found effects of unemployment to be stronger in men and effects of night shift work to be stronger in women. These results provide evidence of associations between unemployment with accelerated ageing and suggest that insecure employment and night work may also increase age acceleration. Our findings have implications for policies relating to current changes in working conditions and highlight the utility of biological age biomarkers in studies in younger populations without long-term health information.

Journal article

Cappozzo A, McCrory C, Robinson O, Freni Sterrantino A, Sacerdote C, Krogh V, Panico S, Tumino R, Iacoviello L, Sieri S, Ricceri F, Chiodini P, McKay GJ, McKnight AJ, Kee F, Young IS, McGuinness B, Crimmins EM, Arpawong TE, Kenny RA, O'Halloran A, Polidoro S, Solinas G, Vineis P, Ieva F, Fiorito Get al., 2022, A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events, Clinical Epigenetics, Vol: 14, ISSN: 1868-7083

Background:Recent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.Results:Using data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived a DNAmCVDscore predictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show that DNAmCVDscore outperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge and DNAmCVDscore was comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).Conclusions:We described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker, DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of

Journal article

Handakas E, Xu Y, Blair Segal A, Huerta MC, Bowman K, Howse LD, Sassi F, Robinson Oet al., 2022, Molecular mediators of the association between child obesity and mental health, Frontiers in Genetics, Vol: 13, Pages: 1-18, ISSN: 1664-8021

Biological mechanisms underlying the association between obesity and depression remain unclear. We investigated the role of metabolites and DNA methylation as mediators of the relationship between childhood obesity and subsequent poor mental health in the English Avon Longitudinal Study of Parents and Children. Obesity was defined according to United Kingdom Growth charts at age 7 years and mental health through the Short Mood and Feelings Questionnaire (SMFQ) completed at age 11 years. Metabolites and DNA methylation were measured by nuclear magnetic resonance spectroscopy and Illumina array in blood at the age of 7 years. The associations between obesity and SMFQ score, as continuous count data or using cut-offs to define depressive symptoms (SMFQ >7) or depression (SMFQ >11), were tested using adjusted Poisson and logistic regression. Candidate metabolite mediators were identified through metabolome-wide association scans for obesity and SMFQ score, correcting for false-discovery rate. Candidate DNA methylation mediators were identified through testing the association of putative BMI-associated CpG sites with SMFQ scores, correcting for look-up false-discovery rate. Mediation by candidate molecular markers was tested. Two-sample Mendelian randomization (MR) analyses were additionally applied to test causal associations of metabolites with depression in independent adult samples. 4,018 and 768 children were included for metabolomics and epigenetics analyses, respectively. Obesity at 7 years was associated with a 14% increase in SMFQ score (95% CI: 1.04, 1.25) and greater odds of depression (OR: 1.46 (95% CI: 0.78, 2.38) at 11 years. Natural indirect effects (mediating pathways) between obesity and depression for tyrosine, leucine and conjugated linoleic acid were 1.06 (95% CI: 1.00, 1.13, proportion mediated (PM): 15%), 1.04 (95% CI: 0.99, 1.10, PM: 9.6%) and 1.06 (95% CI: 1.00, 1.12, PM: 13.9%) respectively. In MR analysis, one unit increase in tyrosine was

Journal article

Fernández-Barrés S, Robinson O, Fossati S, Márquez S, Basagaña X, de Bont J, de Castro M, Donaire-Gonzalez D, Maitre L, Nieuwenhuijsen M, Romaguera D, Urquiza J, Chatzi L, Iakovides M, Vafeiadi M, Grazuleviciene R, Dedele A, Andrusaityte S, Marit Aasvang G, Evandt J, Hjertager Krog N, Lepeule J, Heude B, Wright J, RC McEachan R, Sassi F, Vineis P, Vrijheid Met al., 2022, Urban environment and health behaviours in children from six European countries, Environment International, Vol: 165, ISSN: 0160-4120

Background:Urban environmental design is increasingly considered influential for health and wellbeing, but evidence is mostly based on adults and single exposure studies. We evaluated the association between a wide range of urban environment characteristics and health behaviours in childhood.Methods:We estimated exposure to 32 urban environment characteristics (related to the built environment, traffic, and natural spaces) for home and school addresses of 1,581 children aged 6-11 years from six European cohorts. We collected information on health behaviours including total amount of overall moderate-to-vigorous physical activity, physical activity outside school hours, active transport, sedentary behaviours and sleep duration, and developed patterns of behaviours with principal component analysis. We used an exposure-wide association study to screen all exposure-outcome associations, and the deletion-substitution-addition algorithm to build a final multi-exposure model.Results:In multi-exposure models, green spaces (Normalized Difference Vegetation Index, NDVI) were positively associated with active transport, and inversely associated with sedentary time (22.71 min/day less (95%CI -39.90, -5.51) per interquartile range increase in NDVI). Residence in densely built areas was associated with more physical activity and less sedentary time, and densely populated areas with less physical activity outside school hours and more sedentary time. Presence of a major road was associated with lower sleep duration (-4.80 min/day (95%CI -9.11, -0.48); compared with no major road). Results for the behavioural patterns were similar.Conclusions:This multicohort study suggests that areas with more vegetation, more building density, less population density and without major roads are associated with improved health behaviours in childhood.

Journal article

Robinson O, 2022, Cord blood metabolites and rapid postnatal growth as multiple mediators in the prenatal propensity to childhood overweight, International Journal of Obesity, Vol: 46, Pages: 1384-1393, ISSN: 0307-0565

BACKGROUND: The mechanisms underlying childhood overweight and obesity are poorly known. Here, we investigated the direct and indirect effects of different prenatal exposures on offspring rapid postnatal growth and overweight in childhood, mediated through cord blood metabolites. Additionally, rapid postnatal growth was considered a potential mediator on childhood overweight, alone and sequentially to each metabolite.METHODS: Within four European birth-cohorts (N=375 mother-child dyads), information on seven prenatal exposures (maternal education, pre-pregnancy BMI, weight gain and tobacco smoke during pregnancy, age at delivery, parity, and child gestational age), selected as obesogenic according to a-priori knowledge, was collected. Cord blood levels of 31 metabolites, associated with rapid postnatal growth and/or childhood overweight in a previous study, were measured via liquid-chromatography-quadrupole-time-of-flight-mass-spectrometry. Rapid growth at 12 months and childhood overweight (including obesity) between four and eight years were defined with reference to WHO growth charts. Single mediation analysis was performed using the imputation approach and multiple mediation analysis using the extended-imputation approach.RESULTS: Single mediation suggested that the effect of maternal education, pregnancy weight gain, parity, and gestational age on rapid postnatal growth but not on childhood overweight was partly mediated by seven metabolites, including cholestenone, decenoylcarnitine(C10:1), phosphatidylcholine(C34:3), progesterone and three unidentified metabolites; and the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth. Multiple mediation suggested that the effect of gestational age on childhood overweight was mainly mediated by rapid postnatal growth and that the mediating role of the metabolites was marginal. CONCLUSION: Our findings provide evidence of the involvement of in utero metabolism in the propensity

Journal article

Jarvelin M-R, Wielscher M, Mandaviya PR, Kuehnel B, Joehanes R, Mustafa R, Robinson O, Zhang Y, Bodinier B, Walton E, Mishra PP, Schlosser P, Wilson R, Tsai P-C, Palaniswamy S, Marioni RE, Fiorito G, Cugliari G, Karhunen V, Ghanbari M, Psaty BM, Loh M, Bis JC, Lehne B, Sotoodehnia N, Deary IJ, Chadeau-Hyam M, Brody JA, Cardona A, Selvin E, Smith AK, Miller AH, Torres MA, Marouli E, Gào X, van Meurs JBJ, Graf-Schindler J, Rathmann W, Koenig W, Peters A, Weninger W, Farlik M, Zhang T, Chen W, Xia Y, Teumer A, Nauck M, Grabe HJ, Doerr M, Lehtimäki T, Guan W, Milani L, Tanaka T, Fisher K, Waite LL, Kasela S, Vineis P, Verweij N, van der Harst P, Iacoviello L, Sacerdote C, Panico S, Krogh V, Tumino R, Tzala E, Matullo G, Hurme MA, Raitakari OT, Colicino E, Baccarelli AA, Kähönen M, Herzig K-H, Li S, BIOS consortium, Conneely KN, Kooner JS, Köttgen A, Heijmans BT, Deloukas P, Relton C, Ong KK, Bell JT, Boerwinkle E, Elliott P, Brenner H, Beekman M, Levy D, Waldenberger M, Chambers JC, Dehghan A, Järvelin M-Ret al., 2022, DNA methylation signature of chronic low-gradeinflammation and its role in cardio-respiratorydiseases, Nature Communications, Vol: 13, ISSN: 2041-1723

We performed a multi-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 find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.

Journal article

Freni Sterrantino A, Fiorito G, D'errico A, Oliver R, Virtanen M, Ala-Mursula L, Jarvelin MR, Ronkainen J, Vineis Pet al., 2022, Work-related stress and well-being in association with epigenetic age acceleration: a Northern Finland Birth Cohort 1966 Study, Aging, Vol: 14, Pages: 1128-1156, ISSN: 1945-4589

Recent evidence indicates consistent association of low socioeconomic status with epigenetic age acceleration, measured from DNA methylation. As work characteristics and job stressors are crucial components of socioeconomic status, we investigated their association with various measures of epigenetic age acceleration.The study population included employed and unemployed men and women (n=604) from the Northern Finland Birth Cohort 1966. We investigated the association of job strain, effort-reward imbalance and work characteristics with five biomarkers of epigenetic aging (Hannum, Horvath, PhenoAge, GrimAge, and DunedinPoAm).Our results indicate few significant associations between work stress indicators and epigenetic age acceleration, limited to a range of ±2 years, and smoking recording the highest effect on GrimAge age acceleration biomarker between current and no smokers (median difference 4.73 years (IQR 1.18, 8.41). PhenoAgeAA was associated with job strain active work (β=-1.301 95%CI -2.391, -0.212), slowing aging of less than 1.5 years, and working as white-collar slowed aging six months (GrimAgeAA β=-0.683, 95%CI -1.264, -0.102) when compared to blue collars. Association was found for working for more than 40 hours per week that increased the aging over 1.5 years, (HorvathAA β =2.058 95%CI 0.517,3.599, HannumAA β=1.567, 95%CI 0.415,2.719).The pattern of associations was different between women and men and some of the estimated effects are inconsistent with current literature. Our results provide the first evidence of association of work conditions with epigenetic aging biomarkers. However, further epidemiological research is needed to fully understand how work-related stress affects epigenetic age acceleration in men and women in different societies.

Journal article

Stratakis N, Siskos AP, Papadopoulou E, Nguyen AN, Zhao Y, Margetaki K, Lau C-HE, Coen M, Maitre L, Fernández-Barrés S, Agier L, Andrusaityte S, Basagaña X, Brantsaeter AL, Casas M, Fossati S, Grazuleviciene R, Heude B, McEachan RRC, Meltzer HM, Millett C, Rauber F, Robinson O, Roumeliotaki T, Borras E, Sabidó E, Urquiza J, Vafeiadi M, Vineis P, Voortman T, Wright J, Conti DV, Vrijheid M, Keun HC, Chatzi Let al., 2022, Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health, eLife, Vol: 11, Pages: 1-20, ISSN: 2050-084X

Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used 1H NMR spectroscopy in a multicountry study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, N-methylnicotinic acid, urea, and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food consumption and also had higher capacity in discriminating children’s diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.

Journal article

Keski-Rahkonen P, Robinson O, Alfano R, Plusquin M, Scalbert Aet al., 2022, Commentary: Data processing thresholds for abundance and sparsity and missed biological insights in an untargeted chemical analysis of blood specimens for exposomics, Frontiers in Public Health, Vol: 9, ISSN: 2296-2565

A Commentary onData Processing Thresholds for Abundance and Sparsity and Missed Biological Insights in an Untargeted Chemical Analysis of Blood Specimens for Exposomicsby Barupal, D. K., Baygi, S. F., Wright, R. O., and Arora, M. (2021). Front. Public Health 9:653599. doi: 10.3389/fpubh.2021.653599

Journal article

Alfano R, Robinson O, Handakas E, Nawrot TS, Vineis P, Plusquin Met al., 2022, Perspectives and challenges of epigenetic determinants of childhood obesity: A systematic review, Obesity Reviews, Vol: 23, Pages: 1-13, ISSN: 1467-7881

The tremendous increase in childhood obesity prevalence over the last few decades cannot merely be explained by genetics and evolutionary changes in the genome, implying that gene–environment interactions, such as epigenetic modifications, likely play a major role. This systematic review aims to summarize the evidence of the association between epigenetics and childhood obesity. A literature search was performed via PubMed and Scopus engines using a combination of terms related to epigenetics and pediatric obesity. Articles studying the association between epigenetic mechanisms (including DNA methylation and hydroxymethylation, non-coding RNAs, and chromatin and histones modification) and obesity and/or overweight (or any related anthropometric parameters) in children (0–18 years) were included. The risk of bias was assessed with a modified Newcastle–Ottawa scale for non-randomized studies. One hundred twenty-one studies explored epigenetic changes related to childhood obesity. DNA methylation was the most widely investigated mechanism (N = 101 studies), followed by non-coding RNAs (N = 19 studies) with evidence suggestive of an association with childhood obesity for DNA methylation of specific genes and microRNAs (miRNAs). One study, focusing on histones modification, was identified. Heterogeneity of findings may have hindered more insights into the epigenetic changes related to childhood obesity. Gaps and challenges that future research should face are herein described.

Journal article

Malacarne D, Chandakas E, Robinson O, Pineda E, Saez M, Chatzi L, Fecht Det al., 2022, The built environment as determinant of childhood obesity: a systematic literature review, Obesity Reviews, Vol: 23, Pages: 1-11, ISSN: 1467-7881

We evaluated the epidemiological evidence on the built environment and its link to childhood obesity, focusing on environmental factors such as traffic noise and air pollution, as well as physical factors potentially driving obesity-related behaviours, such as neighbourhood walkability and availability and accessibility of parks and playgrounds. Eligible studies were i) conducted on human children below the age of 18 years, ii) focused on body size measurements in childhood, iii) examined at least one built environment characteristic, iv) reported effect sizes and associated confidence intervals, and v) were published in English language. A z-Test, as alternative to the meta-analysis, was used to quantify associations due to heterogeneity in exposure and outcome definition. We found strong evidence for an association of traffic-related air pollution (nitrogen dioxide and nitrogen oxides exposure; p<0.001) and built environment characteristics supportive of walking (street intersection density; p<0.01 and access to parks; p<0.001) with childhood obesity. We identified a lack of studies which account for interactions between different built environment exposures or verify the role and mechanism of important effect modifiers such as age.

Journal article

Handakas E, Lau CH, Alfano R, Chatzi VL, Plusquin M, Vineis P, Robinson Oet al., 2022, A systematic review of metabolomic studies of childhood obesity: State of the evidence for metabolic determinants and consequences, Obesity Reviews, Vol: 23, Pages: 1-13, ISSN: 1467-7881

Childhood obesity has become a global epidemic and carries significant long-term consequences to physical and mental health. Metabolomics, the global profiling of small molecules or metabolites, may reveal the mechanisms of development of childhood obesity and clarify links between obesity and metabolic disease. A systematic review of metabolomic studies of childhood obesity was conducted, following Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, searching across Scopus, Ovid, Web of Science and PubMed databases for articles published from January 1, 2005 to July 8, 2020, retrieving 1271 different records and retaining 41 articles for qualitative synthesis. Study quality was assessed using a modified Newcastle–Ottawa Scale. Thirty-three studies were conducted on blood, six on urine, three on umbilical cord blood, and one on saliva. Thirty studies were primarily cross-sectional, five studies were primarily longitudinal, and seven studies examined effects of weight-loss following a life-style intervention. A consistent metabolic profile of childhood obesity was observed including amino acids (particularly branched chain and aromatic), carnitines, lipids, and steroids. Although the use of metabolomics in childhood obesity research is still developing, the identified metabolites have provided additional insight into the pathogenesis of many obesity-related diseases. Further longitudinal research is needed into the role of metabolic profiles and child obesity risk.

Journal article

Stratakis N, Siskos AP, Papadopoulou E, Nguyen AN, Zhao Y, Margetaki K, Lau C-HE, Coen M, Maitre L, Fernández-Barrés S, Agier L, Andrusaityte S, Basagaña X, Brantsaeter AL, Casas M, Fossati S, Grazuleviciene R, Heude B, McEachan RRC, Meltzer HM, Millett C, Rauber F, Robinson O, Roumeliotaki T, Borras E, Sabidó E, Urquiza J, Vafeiadi M, Vineis P, Voortman T, Wright J, Conti DV, Vrijheid M, Keun HC, Chatzi Let al., 2021, Author response: Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health

Journal article

Papadopoulou E, Stratakis N, Basagaña X, Brantsæter AL, Casas M, Fossati S, Gražulevičienė R, Småstuen Haug L, Heude B, Maitre L, McEachan RRC, Robinson O, Roumeliotaki T, Sabidó E, Borràs E, Urquiza J, Vafeiadi M, Zhao Y, Slama R, Wright J, Conti DV, Vrijheid M, Chatzi Let al., 2021, Prenatal and postnatal exposure to PFAS and cardiometabolic factors and inflammation status in children from six European cohorts, Environment International, Vol: 157, Pages: 106853-106853, ISSN: 0160-4120

Developing children are particularly vulnerable to the effects of exposure to per- and polyfluoroalkyl substances (PFAS), a group of endocrine disrupting chemicals. We hypothesized that early life exposure to PFASs is associated with poor metabolic health in children. We studied the association between prenatal and postnatal PFASs mixture exposure and cardiometabolic health in children, and the role of inflammatory proteins. In 1,101 mothers-child pairs from the Human Early Life Exposome project, we measured the concentrations of PFAS in blood collected in pregnancy and at 8 years (range = 6-12 years). We applied Bayesian Kernel Machine regression (BKMR) to estimate the associations between exposure to PFAS mixture and the cardiometabolic factors as age and sex- specific z-scores of waist circumference (WC), systolic and diastolic blood pressures (BP), and concentrations of triglycerides (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol. We measured thirty six inflammatory biomarkers in child plasma and examined the underlying role of inflammatory status for the exposure-outcome association by integrating the three panels into a network. Exposure to the PFAS mixture was positively associated with HDL-C and systolic BP, and negatively associated with WC, LDL-C and TG. When we examined the independent effects of the individual chemicals in the mixture, prenatal PFHxS was negatively associated with HDL-C and prenatal PFNA was positively associated with WC and these were opposing directions from the overall mixture. Further, the network consisted of five distinct communities connected with positive and negative correlations. The selected inflammatory biomarkers were positively, while the postnatal PFAS were negatively related with the included cardiometabolic factors, and only prenatal PFOA was positively related with the pro-inflammatory cytokine IL-1beta and WC. Our study supports that prenatal, rather than post

Journal article

Stratakis N, Rock S, La Merrill MA, Saez M, Robinson O, Fecht D, Vrijheid M, Valvi D, Conti DV, McConnell R, Chatzi VLet al., 2021, Prenatal exposure to persistent organic pollutants and childhood obesity: A systematic review and meta-analysis of human studies, Obesity Reviews, Vol: 23, Pages: 1-16, ISSN: 1467-7881

We conducted a systematic review and meta-analysis of the associations between prenatal exposure to persistent organic pollutants (POPs) and childhood obesity. We focused on organochlorines (dichlorodiphenyltrichloroethane [DDT], dichlorodiphenyldichloroethylene [DDE], hexachlorobenzene [HCB], and polychlorinated biphenyls [PCBs]), perfluoroalkyl and polyfluoroalkyl substances (PFAS), and polybrominated diphenyl ethers (PBDEs) that are the POPs more widely studied in environmental birth cohorts so far. We search two databases (PubMed and Embase) through July/09/2021 and identified 33 studies reporting associations with prenatal organochlorine exposure, 21 studies reporting associations with prenatal PFAS, and five studies reporting associations with prenatal PBDEs. We conducted a qualitative review. Additionally, we performed random-effects meta-analyses of POP exposures, with data estimates from at least three prospective studies, and BMI-z. Prenatal DDE and HCB levels were associated with higher BMI z-score in childhood (beta: 0.12, 95% CI: 0.03, 0.21; I2 : 28.1% per study-specific log increase of DDE and beta: 0.31, 95% CI: 0.09, 0.53; I2 : 31.9% per study-specific log increase of HCB). No significant associations between PCB-153, PFOA, PFOS, or pentaPBDEs with childhood BMI were found in meta-analyses. In individual studies, there was inconclusive evidence that POP levels were positively associated with other obesity indicators (e.g., waist circumference).

Journal article

de Prado-Bert P, Ruiz-Arenas C, Vives-Usano M, Andrusaityte S, Cadiou S, Carracedo Á, Casas M, Chatzi L, Dadvand P, González JR, Grazuleviciene R, Gutzkow KB, Haug LS, Hernandez-Ferrer C, Keun HC, Lepeule J, Maitre L, McEachan R, Nieuwenhuijsen MJ, Pelegrí D, Robinson O, Slama R, Vafeiadi M, Sunyer J, Vrijheid M, Bustamante Met al., 2021, The early-life exposome and epigenetic age acceleration in children, Environment International, Vol: 155, ISSN: 0160-4120

The early-life exposome influences future health and accelerated biological aging has been proposed as one of the underlying biological mechanisms. We investigated the association between more than 100 exposures assessed during pregnancy and in childhood (including indoor and outdoor air pollutants, built environment, green environments, tobacco smoking, lifestyle exposures, and biomarkers of chemical pollutants), and epigenetic age acceleration in 1,173 children aged 7 years old from the Human Early-Life Exposome project. Age acceleration was calculated based on Horvath’s Skin and Blood clock using child blood DNA methylation measured by Infinium HumanMethylation450 BeadChips. We performed an exposure-wide association study between prenatal and childhood exposome and age acceleration. Maternal tobacco smoking during pregnancy was nominally associated with increased age acceleration. For childhood exposures, indoor particulate matter absorbance (PMabs) and parental smoking were nominally associated with an increase in age acceleration. Exposure to the organic pesticide dimethyl dithiophosphate and the persistent pollutant polychlorinated biphenyl-138 (inversely associated with child body mass index) were protective for age acceleration. None of the associations remained significant after multiple-testing correction. Pregnancy and childhood exposure to tobacco smoke and childhood exposure to indoor PMabs may accelerate epigenetic aging from an early age.

Journal article

Stratakis N, Siskos AP, Papadopoulou E, Nguyen AN, Zhao Y, Margetaki K, Lau C-HE, Coen M, Maitre L, Fernández-Barrés S, Agier L, Andrusaityte S, Basagaña X, Brantsaeter AL, Casas M, Fossati S, Grazuleviciene R, Heude B, McEachan RRC, Meltzer HM, Millett C, Rauber F, Robinson O, Roumeliotaki T, Borràs E, Sabidó E, Urquiza J, Vafeiadi M, Vineis P, Voortman T, Wright J, Conti DV, Vrijheid M, Keun HC, Chatzi Let al., 2021, Urinary metabolic biomarkers of diet quality in European children are associated with metabolic health, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Urinary metabolic profiling is a promising powerful tool to reflect dietary intake and can help understand metabolic alterations in response to diet quality. Here, we used <jats:sup>1</jats:sup>H-NMR spectroscopy in a multi-country study in European children (1147 children from 6 different cohorts) and identified a common panel of 4 urinary metabolites (hippurate, <jats:italic>N</jats:italic>-methylnicotinic acid, urea and sucrose) that was predictive of Mediterranean diet adherence (KIDMED) and ultra-processed food (UPF) consumption and also had higher capacity in discriminating children’s diet quality than that of established sociodemographic determinants. Further, we showed that the identified metabolite panel also reflected the associations of these diet quality indicators with C-peptide, a stable and accurate marker of insulin resistance and future risk of metabolic disease. This methodology enables objective assessment of dietary patterns in European child populations, complementary to traditional questionary methods, and can be used in future studies to evaluate diet quality. Moreover, this knowledge can provide mechanistic evidence of common biological pathways that characterize healthy and unhealthy dietary patterns, and diet-related molecular alterations that could associate to metabolic disease.</jats:p>

Working paper

Julvez J, Robinson O, 2021, Early life multiple exposures and child cognitive function: a multi-centric birth cohort study in six European countries, Environmental Pollution, Vol: 284, Pages: 1-11, ISSN: 0269-7491

Epidemiological studies mostly focus on single environmental exposures. This study aims to systematically assess associations between a wide range of prenatal and childhood environmental exposures and cognition. The study sample included data of 1298 mother-child pairs, children were 6–11 years-old, from six European birth cohorts. We measured 87 exposures during pregnancy and 122 cross-sectionally during childhood, including air pollution, built environment, meteorology, natural spaces, traffic, noise, chemicals and life styles. The measured cognitive domains were fluid intelligence (Raven's Coloured Progressive Matrices test, CPM), attention (Attention Network Test, ANT) and working memory (N-Back task). We used two statistical approaches to assess associations between exposure and child cognition: the exposome-wide association study (ExWAS) considering each exposure independently, and the deletion-substitution-addition algorithm (DSA) considering all exposures simultaneously to build a final multiexposure model. Based on this multiexposure model that included the exposure variables selected by ExWAS and DSA models, child organic food intake was associated with higher fluid intelligence (CPM) scores (beta = 1.18; 95% CI = 0.50, 1.87) and higher working memory (N-Back) scores (0.23; 0.05, 0.41), and child fast food intake (−1.25; −2.10, −0.40), house crowding (−0.39; −0.62, −0.16), and child environmental tobacco smoke (ETS) (−0.89; −1.42, −0.35), were all associated with lower CPM scores. Indoor PM2.5 exposure was associated with lower N-Back scores (−0.09; −0.16, −0.02). Additional associations in the unexpected direction were found: Higher prenatal mercury levels, maternal alcohol consumption and child higher perfluorooctane sulfonic acid (PFOS) levels were associated with better cognitive performance; and higher green exposure during pregnancy with lower cognitive performance. This fi

Journal article

Stratakis N, Golden-Mason L, Margetaki K, Zhao Y, Valvi D, Garcia E, Maitre L, Andrusaityte S, Basagana X, Borràs E, Bustamante M, Casas M, Fossati S, Grazuleviciene R, Haug LS, Heude B, McEachan RRC, Meltzer HM, Papadopoulou E, Roumeliotaki T, Robinson O, Sabidó E, Urquiza J, Vafeiadi M, Varo N, Wright J, Vos MB, Hu H, Vrijheid M, Berhane KT, Conti DV, McConnell R, Rosen HR, Chatzi Let al., 2021, In utero exposure to mercury is associated with increased susceptibility to liver injury and inflammation in childhood, Hepatology, Vol: 74, Pages: 1546-1559, ISSN: 0270-9139

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant‐associated fatty liver disease. We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother‐child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5‐8.7) from the European Human Early‐Life Exposome (HELIX) cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 μg/L; IQR, 1.1‐3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation‐related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (≥22.1 U/L for females and ≥25.8 U/L for males) and increased concentrations of circulating interleukin (IL)‐1β, IL‐6, IL‐8, and tumor necrosis factor α (TNF‐α). Consistently, inflammatory monocytes exposed in vitro to a physiologically relevant dose of Hg demonstrated significant up‐regulation of genes encoding these four cytokines and increased concentrations of IL‐8 and TNF‐α in the supernatants.Conclusion:These findings suggest that developmental exposure to Hg can contribute to inflammation and increased NAFLD risk in early life.

Journal article

Wielscher M, Mandaviya P, Kuehnel B, Joehanes R, Mustafa R, Robinson O, Zhang T, Bodinier B, Walton E, Mishra P, Schlosser P, Wilson R, Tsai P-C, Palaniswamy S, Marioni R, Fiorito G, Cugliari G, Karhunen V, Ghanbari M, Psaty B, Loh M, Bis J, Lehne B, Sotoodehnia N, Deary I, Chadeau-Hyam M, Brody J, Cardona A, Selvin E, Smith A, Miller A, Torres M, Marouli E, Gào X, Meurs JV, Graf-Schindler J, Rathmann W, Koenig W, Peters A, Weninger W, Farlik M, Zhang Y, Chen W, Xia Y, Teumer A, Nauck M, Grabe H, Dörr M, Lehtimäki T, Guan W, Milani L, Tanaka T, Fischer K, Waite L, Kasela S, Vineis P, Verweij N, Harst PVD, Iacoviello L, Sacerdote C, Panico S, Krogh V, Tumino R, Tzala E, Matullo G, Hurme M, Raitakari O, Colicino E, Baccarelli A, Kähönen M, Herzig K-H, Li S, Heijmans B, Conneely K, Kooner J, Kottgen A, Deloukas P, Relton C, Ong K, Bell J, Boerwinkle E, Elliott P, Brenner H, Beekman M, Levy D, Waldenberger M, Chambers J, Dehghan A, Jarvelin M-Ret al., 2021, DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases, Publisher: Research Square Platform LLC

<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>

Working paper

Maitre L, Julvez J, López-Vicente M, Warembourg C, Tamayo-Uria I, Philippat C, Gützkow KB, Guxens M, Andrusaityte S, Basagaña X, Casas M, de Castro M, Chatzi L, Evandt J, Gonzalez JR, Gražulevičienė R, Smastuen Haug L, Heude B, Hernandez-Ferrer C, Kampouri M, Manson D, Marquez S, McEachan R, Nieuwenhuijsen M, Robinson O, Slama R, Thomsen C, Urquiza J, Vafeidi M, Wright J, Vrijheid Met al., 2021, Early-life environmental exposure determinants of child behavior in Europe: a longitudinal, population-based study, Environment International, Vol: 153, ISSN: 0160-4120

BackgroundEnvironmental exposures in early life influence the development of behavioral outcomes in children, but research has not considered multiple exposures. We therefore aimed to investigate the impact of a broad spectrum of pre- and postnatal environmental exposures on child behavior.Methods and findingsWe used data from the HELIX (Human Early Life Exposome) project, which was based on six longitudinal population-based birth cohorts in Europe. At 6–11 years, children underwent a follow-up to characterize their exposures and assess behavioral problems. We measured 88 prenatal and 123 childhood environmental factors, including outdoor, indoor, chemical, lifestyle and social exposures. Parent-reported behavioral problems included (1) internalizing, (2) externalizing scores, using the child behavior checklist (CBCL), and (3) the Conner’s Attention Deficit Hyperactivity Disorder (ADHD) index, all outcomes being discrete raw counts. We applied LASSO penalized negative binomial regression models to identify which exposures were associated with the outcomes, while adjusting for co-exposures. In the 1287 children (mean age 8.0 years), 7.3% had a neuropsychiatric medical diagnosis according to parent’s reports. During pregnancy, smoking and car traffic showing the strongest associations (e.g. smoking with ADHD index, aMR:1.31 [1.09; 1.59]) among the 13 exposures selected by LASSO, for at least one of the outcomes. During childhood, longer sleep duration, healthy diet and higher family social capital were associated with reduced scores whereas higher exposure to lead, copper, indoor air pollution, unhealthy diet were associated with increased scores. Unexpected decreases in behavioral scores were found with polychlorinated biphenyls (PCBs) and organophosphate (OP) pesticides.ConclusionsOur systematic exposome approach identified several environmental contaminants and healthy lifestyle habits that may influence behavioral problems in children. Modifying

Journal article

Handakas E, Keski-Rahkonen P, Chatzi L, Alfano R, Roumeliotaki T, Plusquin M, Maitre L, Richiardi L, Brescianini S, Scalbert A, Robinot N, Nawrot T, Sassi F, Vrijheid M, Vineis P, Robinson Oet al., 2021, Cord blood metabolic signatures predictive of childhood overweight and rapid growth, International Journal of Obesity, Vol: 45, Pages: 2252-2260, ISSN: 0307-0565

INTRODUCTION:Metabolomics may identify biological pathways predisposing children to risk of overweight and obesity. In this study, we have investigated the cord blood metabolic signatures of rapid growth in infancy and overweight in early childhood in four European birth cohorts.METHODS:Untargeted liquid chromatography-mass spectrometry metabolomic profiles were measured in cord blood from 399 newborns from four European cohorts (ENVIRONAGE, Rhea, INMA and Piccolipiu). Rapid growth in the first year of life and overweight in childhood were defined with reference to WHO growth charts. Metabolome-wide association scans for rapid growth and overweight on over 4500 metabolic features were performed using multiple adjusted logistic mixed effect models and controlling the false discovery rate (FDR) at 5%. Additionally, we performed a look-up analysis of 43 pre-annotated metabolites, previously associated with birthweight or rapid growth. RESULTS:In the MWAS analysis, we identified three and eight metabolites associated with rapid growth and overweight respectively, after FDR correction. Higher levels of cholestenone, a cholesterol derivative produced by microbial catabolism, was predictive of rapid growth (p=1.6x10-3). Lower levels of the branched chain amino acid (BCAA) valine (p=8.6x10-6) was predictive of overweight in childhood. The area under the receiver operator curve for multivariate prediction models including these metabolites and traditional risk factors was 0.77 for rapid growth and 0.82 for overweight, compared to 0.69 and 0.69 respectively for models using traditional risk factors alone. Among the 43 pre-annotated metabolites, seven and five metabolites were nominally associated (P<0.05) with rapid growth and overweight respectively. The BCAA leucine, remained associated (1.6x 0-3) with overweight after FDR correction.CONCLUSION:The metabolites identified here may assist in the identification of children at risk of developing obesity and improve understa

Journal article

McCartney DL, Min JL, Richmond RC, Lu AT, Sobczyk MK, Davies G, Broer L, Guo X, Jeong A, Jung J, Kasela S, Katrinli S, Kuo P-L, Matias-Garcia PR, Mishra PP, Nygaard M, Palviainen T, Patki A, Raffield LM, Ratliff SM, Richardson TG, Robinson O, Soerensen M, Sun D, Tsai P-C, van der Zee MD, Walker RM, Wang X, Wang Y, Xia R, Xu Z, Yao J, Zhao W, Correa A, Boerwinkle E, Dugué P-A, Durda P, Elliott HR, Gieger C, Genetics of DNA Methylation Consortium, de Geus EJC, Harris SE, Hemani G, Imboden M, Kähönen M, Kardia SLR, Kresovich JK, Li S, Lunetta KL, Mangino M, Mason D, McIntosh AM, Mengel-From J, Moore AZ, Murabito JM, NHLBI Trans-Omics for Precision Medicine TOPMed Consortium, Ollikainen M, Pankow JS, Pedersen NL, Peters A, Polidoro S, Porteous DJ, Raitakari O, Rich SS, Sandler DP, Sillanpää E, Smith AK, Southey MC, Strauch K, Tiwari H, Tanaka T, Tillin T, Uitterlinden AG, Van Den Berg DJ, van Dongen J, Wilson JG, Wright J, Yet I, Arnett D, Bandinelli S, Bell JT, Binder AM, Boomsma DI, Chen W, Christensen K, Conneely KN, Elliott P, Ferrucci L, Fornage M, Hägg S, Hayward C, Irvin M, Kaprio J, Lawlor DA, Lehtimäki T, Lohoff FW, Milani L, Milne RL, Probst-Hensch N, Reiner AP, Ritz B, Rotter JI, Smith JA, Taylor JA, van Meurs JBJ, Vineis P, Waldenberger M, Deary IJ, Relton CL, Horvath S, Marioni REet al., 2021, Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging, Genome Biology, Vol: 22, ISSN: 1474-7596

Background:Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.Results:Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.Conclusion:This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.

Journal article

Robinson O, Lau C, 2021, DNA methylation age as a biomarker for cancer, International Journal of Cancer, Vol: 148, Pages: 2652-2663, ISSN: 0020-7136

Cancer is well established as an age‐associated disease, and there is substantial overlap in the molecular, cellular and physiological changes observed with both ageing and the progression of cancer. Age‐specific declines in resilience mechanisms such as DNA repair or epigenetic maintenance may contribute to the development of cancer. These declines may be assessed through biomarkers that measure biological age and through the related concept of “age acceleration”. Epigenetic clocks, assessed through DNA methylation levels, are among the most widely used biological age markers in cancer studies. In this review, we discuss the use of DNA methylation ageing measures to predict population cancer incidence, mortality and survival. Blood‐based DNA methylation age estimators appear to be promising measures of increased cancer risk and mortality, although their reported effects are generally weak, thus its clinical relevance remains to be validated in large case‐cohort and longitudinal studies. Future development of epigenetic and other biological age biomarkers will likely further elucidate the links between ageing and cancer.

Journal article

Robinson O, Carter AR, Aola-Korpela M, Casas JP, Chaturvedi N, Engmann J, Howe LD, Hughes A, Jarvelin MJ, Kahonen M, Karhunen V, Kuh D, Shah T, Ben-Shlomo Y, Sofat R, Lau CE, Lehtimaki T, Menon U, Raitakari O, Ryan A, Providencia R, Smith S, Taylor J, Tillin T, Viikari J, Wong A, Hingorani AD, Kivimaki M, Vineis Pet al., 2021, Metabolic profiles of socioeconomic position: a multi-cohort analysis, International Journal of Epidemiology, Vol: 50, Pages: 768-782, ISSN: 0300-5771

BackgroundLow socioeconomic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. MethodsWe examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles, in approximately 30,000 adults and 4,000 children across ten UK and Finnish cohort studies. ResultsIn risk factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents), and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared to non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids.ConclusionsOur work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavorable metabolic profile, consistent across ages and cohorts. The metabolites we found associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities.

Journal article

Maitre L, Bustamante M, Hernández-Ferrer C, Thiel D, Lau C-H, Siskos A, Vives-Usano M, Ruiz-Arenas C, Robinson O, Mason D, Wright J, Cadiou S, Slama R, Heude B, Gallego-Paüls M, Casas M, Sunyer J, Papadopoulou EZ, Gutzkow KB, Andrusaityte S, Grazuleviciene R, Vafeiadi M, Chatzi L, Sakhi AK, Thomsen C, Tamayo I, Nieuwenhuijsen M, Urquiza J, Borràs E, Sabidó E, Quintela I, Carracedo Á, Estivill X, Coen M, González JR, Keun HC, Vrijheid Met al., 2021, Multi-omics signatures of the human early life exposome

<jats:title>Summary</jats:title><jats:p>Environmental exposures during early life play a critical role in life-course health, yet the molecular phenotypes underlying environmental effects on health are poorly understood. In the Human Early Life Exposome (HELIX) project, a multi-centre cohort of 1,301 mother-child pairs, we associated individual exposomes consisting of &gt;100 chemical, physical and lifestyle exposures assessed in pregnancy and childhood, with multi-omics profiles (methylome, transcriptome, metabolome and proteins) in childhood. We identified 1,170 associations, 249 in pregnancy and 921 in childhood, which revealed potential biological responses and sources of exposure. The methylome best captures the persistent influence of pregnancy exposures, including maternal smoking; while childhood exposures were associated with features from all omics layers, revealing novel signatures for indoor air quality, essential trace elements, endocrine disruptors and weather conditions. This study provides a unique resource (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://helixomics.isglobal.org/">https://helixomics.isglobal.org/</jats:ext-link>) to guide future investigation on the biological effects of the early life exposome.</jats:p>

Journal article

Warembourg C, Nieuwenhuijsen M, Ballester F, de Castro M, Chatzi L, Esplugues A, Heude B, Maitre L, McEachan R, Robinson O, Slama R, Sunyer J, Urquiza J, Wright J, Basagaña X, Vrijheid Met al., 2021, Urban environment during early-life and blood pressure in young children, Environment International, Vol: 146, ISSN: 0160-4120

BackgroundThe urban environment is characterised by many exposures that may influence hypertension development from early life onwards, but there is no systematic evaluation of their impact on child blood pressure (BP).MethodsSystolic and diastolic blood pressure were measured in 4,279 children aged 4–5 years from a multi-centre European cohort (France, Greece, Spain, and UK). Urban environment exposures were estimated during pregnancy and childhood, including air pollution, built environment, natural spaces, traffic, noise, meteorology, and socioeconomic deprivation index. Single- and multiple-exposure linear regression models and a cluster analysis were carried out.ResultsIn multiple exposure models, higher child BP, in particular diastolic BP, was observed in association with higher exposure to air pollution, noise and ambient temperature during pregnancy, and with higher exposure to air pollution and higher building density during childhood (e.g., mean change [95% confidence interval] for an interquartile range increase in prenatal NO2 = 0.7 mmHg[0.3;1.2]). Lower BP was observed in association with higher temperature and better street connectivity during childhood (e.g., temperature = -1.1[-1.6;-0.6]). Some of these associations were not robust in the sensitivity analyses. Mother-child pairs were grouped into six urban environment exposure clusters. Compared to the cluster representing the least harmful urban environment, the two clusters representing the most harmful environment (high in air pollution, traffic, noise, and low in green space) were both associated with higher diastolic BP (1.3[0.1;2.6] and 1.5[0.5;2.5]).ConclusionThis first large systematic study suggests that living in a harmful urban environment may impact BP regulation in children. These findings reinforce the importance of designing cities that promote healthy environments to reduce long-term risk of hypertension and other cardiovascular diseases.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00535749&limit=30&person=true