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Background/Objective: Children’s diets in school-age are inherently unhealthy, with few meeting dietary recommendations. Yet, little is known about similarities and differences on dietary patterns across countries and their association with obesity. We aimed to derive dietary patterns in childhood and explore their association with adiposity-related outcomes in childhood and adolescence. Subjcts/Methods: This study included data from six European countries (Spain, France, UK, Greece, Lithuania and Norway) during childhood (n= 1597) and adolescence (n= 803). Using a food frequency questionnaire, we derived data-driven dietary patterns through exploratory factor analyses and calculated the Mediterranean KIDMED index. We assessed body mass index z-score (zBMI), fat mass proportion and waist-to-height ratio at both visits. Associations were estimated using generalized linear regressions, adjusted for key-confounders. Results: “Meat”, “Dairy”, “Western”, “Healthy” and “Sweets and fats” dietary patterns were derived. Norwegian children showed better diet quality, with higher consumption of fruits and vegetables, and highest “Healthy pattern” adherence, and Lithuanian children, the worst, with higher sweets consumption, and highest “Western pattern” adherence. Children with lower intake of healthy foods (vegetables, fruits, fish) tended to have higher adiposity, e.g., children with average or low “Healthy pattern” adherence (vs. high) had higher fat mass proportion in childhood (average: β (95% CI) 1.44 (0.48; 2.39), low: 1.10 (0.09; 2.12)). Low adherence to a “Healthy pattern” (vs. high) was associated with increased adolescent zBMI, and child and adolescent waist-to-height ratio. Low “Dairy pattern” adherence (vs. high), was associated with lower zBMI and fat mass in childhood, but not in adolescence. No significant associations were seen with the KIDMED index. Conclusions: Many European children have poor diets and a low adherence to a healthy diet pattern may be of concern for adiposity-related outcomes. Assessment of children’s dietary patterns can help tailor dietary advice and provide support for families aiming to prevent future excess weight gain.

The general psychopathology factor (GPF) has been proposed as a way to capture variance shared between psychiatric symptoms. Despite a growing body of evidence showing both genetic and environmental influences on GPF, the biological mechanisms underlying these influences remain unclear. In the current study, we conducted epigenome-wide meta-analyses to identify both probe- and region-level associations of DNA methylation (DNAm) with school-age general psychopathology in six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was examined both at birth (cord blood; prospective analysis) and during school-age (peripheral whole blood; cross-sectional analysis) in total samples of N= 2178 and N= 2190, respectively. At school-age, we identified one probe (cg11945228) located in the Bromodomain-containing protein 2 gene (BRD2) that negatively associated with GPF (p= 8.58 × 10–8). We also identified a significant differentially methylated region (DMR) at school-age (p= 1.63 × 10–8), implicating the SHC Adaptor Protein 4 (SHC4) gene and the EP300-interacting inhibitor of differentiation 1 (EID1) gene that have been previously implicated in multiple types of psychiatric disorders in adulthood, including obsessive compulsive disorder, schizophrenia, and major depressive disorder. In contrast, no prospective associations were identified with DNAm at birth. Taken together, results of this study revealed some evidence of an association between DNAm at school-age and GPF. Future research with larger samples is needed to further assess DNAm variation associated with GPF.

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N= 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r= 0.74, p= 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

ABSTRACTEpimutations are rare alterations of the normal DNA methylation pattern at specific loci, which can lead to rare diseases. Methylation microarrays enable genome-wide epimutation detection, but technical limitations prevent their use in clinical settings: methods applied to rare diseases’ data cannot be easily incorporated to standard analyses pipelines, while epimutation methods implemented in R packages (ramr) have not been validated for rare diseases. We have developed epimutacions, a Bioconductor package (https://bioconductor.org/packages/release/bioc/html/epimutacions.html). epimutacionsimplements two previously reported methods and four new statistical approaches to detect epimutations, along with functions to annotate and visualize epimutations. Additionally, we have developed an user-friendly Shiny app to facilitate epimutations detection (https://github.com/isglobal-brge/epimutacionsShiny) to non-bioinformatician users. We first compared the performance of epimutacionsand ramrpackages using three public datasets with experimentally validated epimutations. Methods in epimutacionshad a high performance at low sample sizes and outperformed methods in ramr. Second, we used two general population children cohorts (INMA and HELIX) to determine the technical and biological factors that affect epimutations detection, providing guidelines on how designing the experiments or preprocessing the data. In these cohorts, most epimutations did not correlate with detectable regional gene expression changes. Finally, we exemplified how epimutacionscan be used in a clinical context. We run epimutacionsin a cohort of children with autism disorder and identified novel recurrent epimutations in candidate genes for autism. Overall, we present epimutacionsa new Bioconductor package for incorporating epimutations detection to rare disease diagnosis and provide guidelines for the design and data analyses.

Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children.

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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, the reported levels of tribromoacetic acid were higher than in other parts of the world. In some regions, the levels of HAAs tended to be peaked in concentration in a different time period than when the levels of THMs peaked. In most epidemiology studies, THMs are used as a surrogate for other halogenated DBPs. This study provides exposure assessment information for epidemiology studies.

Ambient air pollution has been associated with restricted fetal growth, which is linked with adverse respiratory health in childhood. We assessed the effect of maternal exposure to low concentrations of ambient air pollution on birthweight.

Background/aimThere is some evidence that physical activity and nature contact is associated with positive impact on health; however, the research in young children is sparse. The aim of this study was to determine the association between of city park use, residential surrounding greenness level and preschool children health.MethodsThis nested case-control study included 1,489 4–6 years children residents of Kaunas city, Lithuania. Responses to the questionnaires completed by the parents were used to identify children’s health. We assigned individual exposure to greenness levels as GIS assessed the average of satellite-derived Normalised Difference Vegetation Index (NDVI) within a 100 m buffer of each participant address. Using multivariate logistic regression analysis, we estimated the associations of residential greenness in 100 m buffers by median and time spent in nearest city park (more than 5 h/week vs less than 5 h/week) with children health outcome as adjusted odds ratios (aOR) with 95% confidence intervals (CI).ResultsPoor health was reported in 14.0% of children aged 4 to 6 years. Preschool children who spent shorter than 5 h/week in city park had statistically significant by 48% higher risk (OR 1.48 95% CI: 1.10–2.02) of poor health than those who spent longer than 5 hours per week. With reference to the group of higher level of residential greenness exposure (NDVI >median and time spent in city park >5 h/week), lower level of greenness exposure and shorter time spent in city park were associated with statistically significant higher adjusted odds ratios for poor health in 4–6 year-old children (aOR 2.35; 95% CI: 1.45 to 3.81).ConclusionThe findings of this study suggest a beneficial impact of use of city parks on poor health amongst 4–6 year-old children and demonstrate the important role that increased residential greenness can play a beneficial role in reducing the risk of young children’s poor health.