Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Abstract 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 ass…

Urban environment during early-life and blood pressure in young children

Background: The 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). Methods: Systolic 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. Results: In multi…

Drinking water disinfection by-products, genetic polymorphisms, and birth outcomes in a european mother-child cohort study

Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. Methods: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle-and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and e…

Additional file 4 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 4. Assessment of genomic inflation and heterogeneity.

Mechanisms of the Development of Allergy (MeDALL) : Introducing novel concepts in allergy phenotypes

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Q…

WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Variations in the prevalence of childhood asthma and wheeze in MeDALL cohorts in Europe.

While there is evidence for variations in prevalence rates of childhood wheeze and asthma between countries, longitudinal, individual-level data are needed to understand these differences. The aim of this study was to examine variations in prevalence rates of childhood asthma, wheeze and wheeze with asthma in Europe. We analysed datasets from 10 MeDALL (Mechanisms of the Development of ALLergy) cohorts in eight countries, representing 26 663 children, to calculate prevalence rates of wheeze and asthma by child age and wheeze with asthma at age 4 years. Harmonised variables included outcomes parent-reported wheeze and parent-reported doctor-diagnosed asthma, and covariates maternal education…

Additional file 3 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 3. Supplementary Figures - Figures S1-S31.

Prenatal exposure to phenols and lung function, wheeze, and asthma in school-age children from 8 European birth cohorts

Prenatal exposure to phenolic compounds, widely used in many consumer products, can alter lung development and increase the risk of respiratory disorders in the offspring. However, evidence is scarce and mostly focused on bisphenol-A (BPA), although there are other substitutes that could also interfere with the developing respiratory system. We aim to estimate the association between exposure to 5 phenols during pregnancy (BPA, BPAF, BPB, BPF, and BPS) and lung function, wheeze, and asthma in school-age children. We included 2685 mother-child pairs from 8 European birth cohorts. Phenols concentrations were determined in urinary maternal samples collected during pregnancy (1999-2010). Betwee…

Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

Urban environment and cognitive and motor function in children from four European birth cohorts

[EN]Background: The urban environment may influence neurodevelopment from conception onwards, but there is no evaluation of the impact of multiple groups of exposures simultaneously. We investigated the association between early-life urban environment and cognitive and motor function in children. Methods: We used data from 5403 mother-child pairs from four population-based birth-cohorts (UK, France, Spain, and Greece). We estimated thirteen urban home exposures during pregnancy and childhood, including: built environment, natural spaces, and air pollution. Verbal, non-verbal, gross motor, and fine motor functions were assessed using validated tests at five years old. We ran adjusted multi-e…

Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

Severe Chronic Allergic (and Related) Diseases: A Uniform Approach – A MeDALL – GA<sup>2</sup>LEN – ARIA Position Paper

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in …

Urban environment during early-life and blood pressure in children

Background. The urban environment is characterised by many exposures that may influence hypertension development, but studies evaluating multiple urban exposures from pregnancy onwards are lacking....

Additional file 1 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 1. Individual cohort descriptions and acknowledgements.

DNA methylation in childhood asthma

Background: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. Methods: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4–5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design. After identification of differentially m…

Additional file 5 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 5. Colocalization plots.

Additional file 6 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 6. Review history.

Associations between air pollution and pediatric eczema, rhinoconjunctivitis and asthma: A meta-analysis of European birth cohorts

Background: Uncertainly continues to exist regarding the role of air pollution on pediatric asthma and allergic conditions, especially as air pollution levels have started to decrease in recent decades. Objective: We examined associations of long-term air pollution levels at the home address with pediatric eczema, rhinoconjunctivitis and asthma prevalences in five birth cohorts (BIB, EDEN, GASPII, RHEA and INMA) from seven areas in five European countries. Methods: Current eczema, rhinoconjunctivitis and asthma were assessed in children aged four (N = 6527) and eight years (N = 2489). A multi-morbidity outcome (≥2 conditions versus none) was also defined. Individual outdoor levels of nitrog…

Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing

AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts

ObjectiveTo assess the separate and combined associations of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta‐analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre‐pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre‐eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre‐pregnancy BMI and gesta…

Understanding the complexity of IgE-related phenotypes from childhood to young adulthood: A Mechanisms of the Development of Allergy (MeDALL) seminar.

Mechanisms of the Development of Allergy (MeDALL), a Seventh Framework Program European Union project, aims to generate novel knowledge on the mechanisms of initiation of allergy. Precise phenotypes of IgE-mediated allergic diseases will be defined in MeDALL. As part of MeDALL, a scientific seminar was held on January 24, 2011, to review current knowledge on the IgE-related phenotypes and to explore how a multidisciplinary effort could result in a new integrative translational approach. This article provides a summary of the meeting. It develops challenges in IgE-related phenotypes and new clinical and epidemiologic approaches to the investigation of allergic phenotypes, including cluster a…

Overview of the JET results in support to ITER

The 2014–2016 JET results are reviewed in the light of their significance for optimising the ITER research plan for the active and non-active operation. More than 60 h of plasma operation with ITER first wall materials successfully took place since its installation in 2011. New multi-machine scaling of the type I-ELM divertor energy flux density to ITER is supported by first principle modelling. ITER relevant disruption experiments and first principle modelling are reported with a set of three disruption mitigation valves mimicking the ITER setup. Insights of the L–H power threshold in Deuterium and Hydrogen are given, stressing the importance of the magnetic configurations and the recent m…

Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America

Background Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. Methods and findings We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/bir…

Occurrence of DBPs in Drinking Water of European Regions for Epidemiology Studies

International audience; A three-year study was conducted on the occurrence of disinfection by-products (DBPs) - trihalomethanes (THMs), haloacetic acids (HAAs), and haloacetonitriles - in drinking water of regions of Europe where epidemiology studies were being carried out. Thirteen systems in six countries (i.e., Italy, France, Greece, Lithuania, Spain, United Kingdom) were sampled. Typically chlorinated DBPs dominated. However, in most of Catalonia (Spain) and in Heraklion (Greece), brominated DBPs dominated. The degree of bromine incorporation into the DBP classes was in general similar among them. This is important, as brominated DBPs are a greater health concern. In parts of Catalonia,…

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood: An individual participant data meta-analysis

Background Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. Methods and findings We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, No…

Paving the way of systems biology and precision medicine in allergic diseases: the Me DALL success story

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sen…

Influence of the Urban Exposome on Birth Weight

Background: The exposome is defined as the totality of environmental exposures from conception onwards. It calls for providing a holistic view of environmental exposures and their effects on human health by evaluating multiple environmental exposures simultaneously during critical periods of life. Objective: We evaluated the association of the urban exposome with birth weight. Methods: We estimated exposure to the urban exposome, including the built environment, air pollution, road traffic noise, meteorology, natural space, and road traffic (corresponding to 24 environmental indicators and 60 exposures) for nearly 32,000 pregnant women from six European birth cohorts. To evaluate associatio…

Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second c…

The Urban Exposome during Pregnancy and Its Socioeconomic Determinants

Background: The urban exposome is the set of environmental factors that are experienced in the outdoor urban environment and that may influence child development. Objective: The authors’ goal was to describe the urban exposome among European pregnant women and understand its socioeconomic determinants. Methods: Using geographic information systems, remote sensing and spatio-temporal modeling we estimated exposure during pregnancy to 28 environmental indicators in almost 30,000 women from six population-based birth cohorts, in nine urban areas from across Europe. Exposures included meteorological factors, air pollutants, traffic noise, traffic indicators, natural space, the built environment…

Environmental Risk Score of subclinical Psychopathology risk in children

Current knowledge on environmental causation for psychiatric disorders suggests a complex picture with a multitude of social, physical and chemical exposures occurring at different stages of life. ...

Shared DNA methylation signatures in childhood allergy: The MeDALL study

Contains fulltext : 232514.pdf (Publisher’s version ) (Open Access) BACKGROUND: Differential DNA methylation associated with allergy might provide novel insights into the shared or unique etiology of asthma, rhinitis, and eczema. OBJECTIVE: We sought to identify DNA methylation profiles associated with childhood allergy. METHODS: Within the European Mechanisms of the Development of Allergy (MeDALL) consortium, we performed an epigenome-wide association study of whole blood DNA methylation by using a cross-sectional design. Allergy was defined as having symptoms from at least 1 allergic disease (asthma, rhinitis, or eczema) and positive serum-specific IgE to common aeroallergens. The discove…

Cabbage and fermented vegetables: from death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

International audience; Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1 R) axis associated with oxidative stress. This leads to insulin resistance …

Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 2. Supplementary Tables -Tables S1-S31.

Additional file 2 of Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Additional file 2. Supplementary Tables -Tables S1-S31.