Analysis of DNA methylation at birth and in childhood reveals changes associated with season of birth and latitude

This is the final version. Available from BMC via the DOI in this record. Individual cohort-level data can be obtained from the respective cohort (see Additional file 1: Table S1 and Additional file 2 for cohort details).BACKGROUND: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear. METHODS: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points. RESULTS: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N). CONCLUSIONS: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes.Wellcome TrustBiotechnology and Biological Sciences Research Council (BBSRC)Biotechnology and Biological Sciences Research Council (BBSRC)European Union’s Horizon 2020Economic and Social Research Council (ESRC)Medical Research Council (MRC)Medical Research Council (MRC)European UnionSwedish foundation for strategic research (SSF)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)Environmental Protection Agency (EPA)National Cancer Institute Cancer CenterNational Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)Environmental Protection Agency (EPA)Environmental Protection Agency (EPA)European UnionEuropean UnionEuropean UnionEuropean UnionEuropean Union’s Horizon 2020European Research Council (ERC)German Ministry of Education and ResearchNational Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)Autism SpeaksNational Institutes of Health (NIH)National Institutes of Health (NIH)European UnionEuropean UnionEuropean UnionEuropean UnionEuropean UnionEuropean UnionEuropean UnionEuropean UnionEuropean UnionEuropean Research Council (ERC)Flemisch Scientific Research CouncilFlemisch Scientific Research CouncilFlemisch Scientific Research CouncilEuropean UnionFonds de recherche du Québec - Santé (FRQS)Canadian Institute of Health Research (CIHR)Canadian Institute of Health Research (CIHR)Netherlands Organisation for Scientific Research (NWO)National Institute of Child and Human DevelopmentEuropean Union’s Horizon 2020European Union’s Horizon 2020European Union’s Horizon 2020ZonMwZonMwMedical Research Council Integrative Epidemiology Unit (University of Bristol)Netherlands Heart FoundationNetherlands Heart FoundationNetherlands Organisation for Scientific Research (NWO)European UnionNational Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)Spanish Ministry of ScienceNational Institute for Health and Care Research (NIHR)Wellcome TrustNorwegian Ministry of Health and the Ministry of Education and ResearchNorwegian Ministry of Health and the Ministry of Education and ResearchNorwegian Ministry of Health and the Ministry of Education and ResearchLithuanian Agency for Science Innovation and TechnologySpanish Ministry of HealthSpanish Ministry of HealthSpanish Ministry of HealthSpanish Ministry of HealthSpanish Ministry of HealthInstituto de Salud Carlos IIIInstituto de Salud Carlos IIIEuropean Research Council (ERC)CDMRP/Department of DefenseNIGMSNational Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Asthma Campaign, UKNational Institutes of Health (NIH)Medical Research Council (MRC)National Institutes of Health (NIH)Norwegian Research CouncilNational Institute of Environmental Health SciencesResearch Council of NorwayNational Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesSwedish Research CouncilSwedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)National Institutes of Health (NIH)Medical Research Council Integrative Epidemiology Unit (University of Bristol)Medical Research Council Integrative Epidemiology Unit (University of Bristol)Medical Research Council Integrative Epidemiology Unit (University of Bristol)Swedish Heart-Lung FoundationUniversity of MunichFoundation for Medical Research (FRM)National Agency for ResearchNational Institute for Research in Public HealthFrench Ministry of HealthFrench Ministry of ResearchInserm Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research ProgramsParis–Sud UniversityNestléFrench National Institute for Population Health SurveillanceFrench National Institute for Health EducationFrench Agency for Environmental Health SafetyMutuelle Générale de l’Education NationaleFrench National Agency for Food SecurityFrench-speaking association for the study of diabetes and metabolismItalian National Centre for Disease Prevention and ControlItalian Ministry of HealthGreek Ministry of HealthFlemish Government (Department of Economy, Science and Innovations, Agency for Care and Health and Department of Environment)The Research Foundation-FlandersFlemish Institute for Technological ResearchDiabète QuébecErasmus University RotterdamNetherlands Organization for Health Research and Development and the Ministry of Health, Welfare and SportErasmus MCDanish National Research FoundationDanish Regional CommitteesNovo Nordisk FoundationLundbeck FoundationHelmholtz Center for Environmental ResearchGerman Cancer Research CentreAcademy of FinlandEraNetEVOUniversity of Helsinki Research FundsSigne and Ane Gyllenberg foundationEmil Aaltonen FoundationFinnish Medical FoundationJane and Aatos Erkko FoundationJuho Vainio foundationYrjö Jahnsson foundationJalmari and Rauha Ahokas foundationPaivikki and Sakari Sohlberg FoundationSigrid Juselius FoundationSir Jules Thorn Charitable TrustSwedish Asthma and Allergy Association's Research FoundationStiftelsen Frimurare Barnhuset Stockhol

Maternal educational attainment in pregnancy and epigenome-wide DNA methylation changes in the offspring from birth until adolescence

This is the final version. Available on open access from Springer Nature via the DOI in this recordData availability: Meta-analysis results files will be deposited in the EWAS Catalogue data repository (http://ewascatalog.org) upon publication.Maternal educational attainment (MEA) shapes offspring health through multiple potential pathways. Differential DNA methylation may provide a mechanistic understanding of these long-term associations. We aimed to quantify the associations of MEA with offspring DNA methylation levels at birth, in childhood and in adolescence. Using 37 studies from high-income countries, we performed meta-analysis of epigenome-wide association studies (EWAS) to quantify the associations of completed years of MEA at the time of pregnancy with offspring DNA methylation levels at birth (n = 9 881), in childhood (n = 2 017), and adolescence (n = 2 740), adjusting for relevant covariates. MEA was found to be associated with DNA methylation at 473 cytosine-phosphate-guanine sites at birth, one in childhood, and four in adolescence. We observed enrichment for findings from previous EWAS on maternal folate, vitamin-B12 concentrations, maternal smoking, and pre-pregnancy BMI. The associations were directionally consistent with MEA being inversely associated with behaviours including smoking and BMI. Our findings form a bridge between socio-economic factors and biology and highlight potential pathways underlying effects of maternal education. The results broaden our understanding of bio-social associations linked to differential DNA methylation in multiple early stages of life. The data generated also offers an important resource to help a more precise understanding of the social determinants of health

Domestic exposure to volatile organic compounds in relation to asthma and allergy in children and adults

Over the past decades, the prevalence of asthma, allergic disease and atopy has increased significantly and in parallel with the increased use of products and materials emitting volatile organic compounds (VOCs) in the indoor environment. The purpose of this review is to examine the evidence of the relationship between quantitatively measured domestic exposure to VOCs and allergic diseases and allergy in children and adults. Sources, potential immune-inflammatory mechanisms and risks for development and severity of asthma and allergy have been addressed. Available evidence is based on studies that have mainly used observational designs of variable quality. Total, aromatic, aliphatic, microbial VOCs and aldehydes have been the most widely investigated VOC classes, with formaldehyde being the most commonly examined single compound. Overall, the evidence is inadequate to draw any firm conclusions. However, given indicative evidence from a few high-quality studies and significant potential for improvements in asthma outcomes in those with established disease, there is a need to consider undertaking further investigation of the relationship between domestic VOC exposure and asthma/allergy outcomes that should encompass both high-quality, robust observational studies and ultimately clinical trials assessing the impact of interventions that aim to reduce VOC exposure in children and adults with asthma