Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Gruzieva, Olena; Xu, Cheng‐Jian; Yousefi, Paul; Relton, Caroline L; Merid, Simon Kebede; Breton, Carrie V.; Gao, Lu; Volk, Heather E.; Feinberg, Jason I.; Ladd‐Acosta, Christine; Bakulski, Kelly M.; Auffray, Charles; Lemonnier, Nathanaël; Plusquin, Michelle; Ghantous, Akram; Herceg, Zdenko; Nawrot, Tim S.; Pizzi, Costanza; Richiardi, Lorenzo; Rusconi, Franca; Víneis, Paolo; Kogevinas, Manolis; Felix, Janine F.; Duijts, Liesbeth; Dekker, Herman T. den; Jaddoe, Vincent W. V.; Ruiz, José Luis; Bustamante, Mariona; Antó, Josep M.; Sunyer, Jordi; Vrijheid, Martine; Gützkow, Kristine B.; Gražulevičienė, Regina; Hernández-Ferrer, Carles; Annesi‐Maesano, Isabella; Lepeule, Johanna; Bousquet, Jean; Bergström, Anna; Kull, Inger; Söderhäll, Cilla; Kere, Juha; Gehring, Ulrike; Brunekreef, Bert; Just, Allan C.; Wright, Rosalind J.; Peng, Cheng; Gold, Diane R.; Kloog, Itai; DeMeo, Dawn L.; Pershagen, Göran; Koppelman, Gerard H.; London, Stephanie J.; Baccarelli, Andrea A.; Melén, Erik

doi:10.1289/ehp4522

Cited by 121 publications

(91 citation statements)

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“…The best studied epigenetic modification is methylation. DNA methylation patterns have been associated with environmental factors relevant to preterm birth, including smoking, air pollution exposure, microbial and maternal nutritional factors [18][19][20][21][22]. Such exposure-related epigenetic patterns potentially influence gene expression profiles and/or susceptibility to chronic disease during the lifecourse [23,24].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

et al. 2020

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Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina’s HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4–18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27–42 weeks), at Bonferroni significance, P < 1.06 × 10− 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

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Section: Introductionmentioning

confidence: 99%

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

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“…Early-life stressors, including socio-economic, migration, urban environmental, and lifestyle related factors, have been associated with cardio-metabolic, respiratory, and mental health and disease, which together contribute greatly to the global burden of non-communicable diseases [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. An accumulating body of evidence suggests that exposure to these factors during fetal life and childhood affects later life health trajectories [38].…”

Section: Integrated Early-life Stressors Approach and The Exposomementioning

confidence: 99%

“…Results from well-performed individual participant data meta-analyses suffer less from publication bias than meta-analyses based on published data. Multiple individual participant data meta-analyses on environmental exposures, lifestyle related and (epi)genetic associations have already been published as part of birth cohort collaborations [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

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The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

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Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socioeconomic , and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.

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“…Furthermore, urban populations show increased levels of mitochondrial methylation genes due to PM exposure ( 201 ). There is evidence of the existence of methylation, acetylation and phosphorylation of histones H3 and H4, markers found in genes involved in the activation of immune cells and cardiovascular diseases ( 200 , 202 – 205 ). Altogether, air pollutants can generate DNA adducts promoting carcinogenesis and deteriorate telomerase activity, as reviewed by Martens and Nawrot (2016), and contributing to continuous DNA damage and premature aging ( 206 , 207 ).…”

Section: Induction Of An Uncontrolled Inflammatory Process By Air Polmentioning

confidence: 99%

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

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The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5–8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual’s sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging.

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Prenatal Particulate Air Pollution and DNA Methylation in Newborns: An Epigenome-Wide Meta-Analysis

Cited by 121 publications

References 58 publications

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease

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