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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, socio-economic, 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. ; The LifeCycle project received funding from the European Union's Horizon 2020 research and innovation programme (Grant Agreement No. 733206 LifeCycle). All study specific acknowledgements and funding are presented in the supplementary materials. This manuscript reflects only the author's view and the Commission is not responsible for any use that may be made of the information it contains

Background: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. Objectives: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). Methods: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. Results: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). Conclusion: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth. ; Per cohort. ABIS: Data used for this research was provided by the Cohort Study, which is supported in part by JDRF-Wallenberg foundations (K 98-99D-12813-01A), the Swedish Medical Research Council (MFR; Vetenskapsrådet; K99-72X-11242-05A), the Swedish Child Diabetes Foundation (Barndiabetesfonden), and the Swedish Diabetes Association, Medical Research Council of South East Sweden (FORSS), Novo Nordisk Foundation, Prevention of Diabetes, and its Complications Strategic Area-LiU. ALSPAC: We are extremely grateful to all the families who took part in the study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionist, and nurses. The UK Medical Research Council and the Wellcome Trust (grant reference 092731) and the University of Bristol provide core support for ALSPAC. BILD: Data used for this research were provided by the Cohort Study, which is supported in part by funds of the Swiss National Science Foundation; the European Respiratory Society (ERS); the Austrian, German and Swiss Paediatric respiratory Society; and the Swiss Governmental Anti-Tobacco Fund. CONER: Data used for this research were provided by the Cohort Study, which is supported in part by funds of the Italian ministry of health. COPSAC: COPSAC is funded by private and public research funds listed on www.copsac.com. The Lundbeck Foundation, the Danish Strategic Research Council, the Pharmacy Foundation of 1991, the Augustinus Foundation, the Danish Medical Research Council, and the Danish Pediatric Asthma Centre provided the core support for the COPSAC research center. No pharmaceutical company was involved in the study. The funding agencies did not have any role in design and conduct of the study; collection, management, and interpretation of the data; or preparation, review, or approval of the manuscript. CZECH: Data used for this research was provided by the Cohort Study, which is supported in part by funds of the Ministry of Environment of the Czech Republic (SP/1b3/8/08). DNBC: The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, and the Augustinus Foundation. EDEN: We acknowledge all the funding sources for the EDEN study: Fondation pour la Recherche Médicale (FRM), the French Ministry of Research: IFR program, the INSERM Nutrition Research program, the French Ministry of Health Perinatality Program, the French Agency for Environment security (AFFSET), the French National Institute for Population Health Surveillance (INVS), Paris-Sud University, the French National Institute for Health Education (INPES), Nestlé, Mutuelle Générale de l'Education Nationale {MGEN), the French-speaking Association for the Study of Diabetes and Metabolism (Alfediam), and the National Agency for Research (ANR). GASPII: Data used for this research was provided by the Cohort Study, which is supported in part by funds of the Italian Ministry of Health, 2001. GECKO Drenthe: The GECKO Drenthe cohort is supported and funded by an unrestricted grant from Hutchison Whampoa, the University of Groningen, and Well Baby Clinic Foundation Icare. GENERATION R: The Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; and the Netherlands Organization for Health Research and Development. The researchers are independent from the funders. The study sponsors had no role in study design, data analysis, interpretation of data, or writing of this report. Additional support was available from the Netherlands Organization for Health Research and Development (VIDI) and the Dutch Asthma Foundation. GENERATION XXI: Data used for this research were provided by the Cohort Study, which is supported in part by funds of the Programa Operacional de Saúde–Saúde XXI, Quadro Comunitário de Apoio III (FEDER), the Northern Regional Administration of Health, the Portuguese Foundation for Science and Technology (PTDC/SAUESA/105033/2008), and the Calouste Gulbenkian Foundation. HUMIS: The research leading to these results has received funding from the Norwegian Research Council under grant agreement 213148 (MILPAAHEL) and the European Union's Seventh Framework Programme (FP7/2007-2013), project Early Nutrition under grant agreement number 289346, and project OBELIX under grant agreement number 22739. INMA: Gipuzkoa/Sabadell/Valencia/Menorca Data used for this research were provided by the INMA–Environment and Childhood Project (www.proyectoinma.org), which is supported in part by funds. This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041), the Spanish Ministry of Health (FIS- PI041436, PI042018, PI06/0867 PI07/0252, PI081151, and PI09/02311,and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/02647), Generalitat de Catalunya-CIRIT 1999SGR 00241, the Conselleria de Sanitat Generalitat Valenciana, the Department of Health of the Basque Government (2005111093 and 2009111069), the Provincial Government of Gipuzkoa (DFG06/004 and DFG08/001), Obra Social Cajastur, Universidad de Oviedo, the EU Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), Consejería de Salud de la Junta de Andalucía (grant number 183/07), and Fundació Roger Torné. ISLE OF WIGHT: Data used for this research were provided by the Cohort Study, which is supported in part by funds of the National Institute of Health, the British Medical Association, and David Hide Asthma and Allergy Research Centre Trustees. KOALA: Data used for this research were provided by the Cohort Study, which is supported in part by funds from the Netherlands Asthma Foundation (grant nos. 3.2.03.48 and 3.2.07.022). LEICESTER 1990/1998: Data used for this research were provided by the Leicester Cohort Studies, which are supported by funds from Asthma UK (grant no. 07/048), the Swiss National Science Foundation (grant no. 32003B-144068), the Wellcome Trust, and many others. LIFEWAYS: Data used for this research were provided by the Cohort Study, which is supported in part by funds of the Health Research Board, Republic of Ireland. MAS: Data for this research question were obtained by the study centre of the cohort study. The Multicentre Allergy Study (1990) was supported by grants from the German Federal Ministry for Education and Research (BMBF) under reference numbers 07015633, 07 ALE 27, 01EE9405/5, and 01EE9406.NINFEA: Data used for this research were provided by the Cohort Study, which is supported in part by funds of Compagnia di SanPaolo Foundation, Piedmont Region, and the Italian Ministry of University and Research. PCB: Data used for this research was provided by the Cohort Study, which is supported in part by funds from National Institutes of Health grant R01-CA096525 and EU project OBELIX (no. 227391). PIAMA: The PIAMA study has been funded by the Netherlands Organization for Health Research and Development; the Netherlands Organization for Scientific Research; the Netherlands Asthma Fund; the Netherlands Ministry of Spatial Planning, Housing, and the Environment; and the Netherlands Ministry of Health, Welfare and Sport. REPRO PL: Data used for this research were provided by the Cohort Study, which is supported in part by funds from the National Center for Research and Development, Poland (grant no. PBZ-MEiN-/8/2//2006; contract no. K140/P01/2007/1.3.1.1.) and grant PNRF-218-AI-1/07 from Norway through the Norwegian Financial Mechanism within the Polish-Norwegian Research Fund. RHEA: Data used for this research were provided by the Cohort Study, which is supported in part by funds of European Commission. SEATON: Data used for this research were provided by the university, which is supported in part by funds from Asthma UK and the Medical Research Council. SWS: The Southampton Women's Survey is supported by grants from the Medical Research Council, the British Heart Foundation, the Food Standards Agency, the British Lung Foundation, Arthritis Research UK, NIHR Southampton Biomedical Research Centre, the University of Southampton and University Hospital Southampton NHS Foundation Trust, and the Commission of the European Community, specific RTD Programme "Quality of Life and Management of Living Resources," within the 7th Framework Programme, research grant no. FP7/2007-13 (Early Nutrition Project). This manuscript does not necessarily reflect the views of the funders and in no way anticipates the future policy in this area. WHISTLER: Data used for this research were provided by the Cohort Study, which is supported in part by funds from the Netherlands Organization for health Research and Development (ZON-MW), the University Medical Center Utrecht, and an unrestricted research grant from GlaxoSmithKline, The Netherlands

Background: Infant weight gain is associated with lower lung function and a higher risk of childhood asthma. Detailed individual childhood growth patterns might be better predictors of childhood respiratory morbidity than the difference between two weight and height measurements. We assessed the associations of early childhood growth patterns with lung function and asthma at the age of 10 years and whether the child's current body mass index (BMI) influenced any association. Methods: We derived peak height and weight growth velocity, BMI at adiposity peak, and age at adiposity peak from longitudinally measured weight and height data in the first 3 years of life of 4435 children enrolled in a population-based prospective cohort study. At 10 years of age, spirometry was performed and current asthma was assessed by questionnaire. Spirometry outcomes included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and forced expiratory flow after exhaling 75% of vital capacity (FEF75). Results: Greater peak weight velocity was associated with higher FVC but lower FEV1/FVC and FEF75. Greater BMI at adiposity peak was associated with higher FVC and FEV1 but lower FEV1/FVC and FEF75. Greater age at adiposity peak was associated with higher FVC, FEV1, FEV1/FVC and FEF75, particularly in children with a small size at birth, and lower odds of current asthma in boys. The child's current BMI only explained the associations of peak weight velocity and BMI at adiposity peak with FVC and FEV1. Peak height velocity was not consistently associated with impaired lung function or asthma. Conclusion: Peak weight velocity and BMI at adiposity peak were associated with reduced airway patency in relation to lung volume, whereas age at adiposity peak was associated with higher lung function parameters and lower risk of asthma at 10 years, particularly in boys. ; The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Liesbeth Duijts received additional funding from the European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no. 696295; 2017), ZonMW The Netherlands (no. 529051014; 2017)). The study was supported by the Netherlands Organization for Health Research and Development (VIDI 016.136.361), a European Research Council Consolidator Grant (ERC-2014-CoG-648916), funding from the European Union's Seventh Framework Programme under grant agreement no. 289346 (EarlyNutrition), and funding from the European Union's Horizon 2020 research and innovation programme under grant agreements no. 733206 (LifeCycle) and no. 633595 (DynaHEALTH). Dr Maribel Casas received funding from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) (CD12/00563 and MS16/00128). The researchers are independent from the funders.

Background: Prenatal inflammation has been proposed as an important mediating factor in several adverse pregnancy outcomes. C-reactive protein (CRP) is an inflammatory cytokine easily measured in blood. It has clinical value due to its reliability as a biomarker for systemic inflammation and can indicate cellular injury and disease severity. Elevated levels of CRP in adulthood are associated with alterations in DNA methylation. However, no studies have prospectively investigated the relationship between maternal CRP levels and newborn DNA methylation measured by microarray in cord blood with reasonable epigenome-wide coverage. Importantly, the timing of inflammation exposure during pregnancy may also result in different effects. Thus, our objective was to evaluate this prospective association of CRP levels measured during multiple periods of pregnancy and in cord blood at delivery which was available in one cohort (i.e., Effects of Aspirin in Gestation and Reproduction trial), and also to conduct a meta-analysis with available data at one point in pregnancy from three other cohorts from the Pregnancy And Childhood Epigenetics consortium (PACE). Secondarily, the impact of maternal randomization to low dose aspirin prior to pregnancy on methylation was assessed. Results: Maternal CRP levels were not associated with newborn DNA methylation regardless of gestational age of measurement (i.e., CRP at approximately 8, 20, and 36 weeks among 358 newborns in EAGeR). There also was no association in the meta-analyses (all p > 0.5) with a larger sample size (n = 1603) from all participating PACE cohorts with available CRP data from first trimester (< 18 weeks gestation). Randomization to aspirin was not associated with DNA methylation. On the other hand, newborn CRP levels were significantly associated with DNA methylation in the EAGeR trial, with 33 CpGs identified (FDR corrected p < 0.05) when both CRP and methylation were measured at the same time point in cord blood. The top 7 CpGs most strongly associated with CRP resided in inflammation and vascular-related genes. Conclusions: Maternal CRP levels measured during each trimester were not associated with cord blood DNA methylation. Rather, DNA methylation was associated with CRP levels measured in cord blood, particularly in gene regions predominately associated with angiogenic and inflammatory pathways. ; This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA), and the EAGeR trial was specifically funded under contract numbers HHSN267200603423, HHSN267200603424, HHSN267200603426, and HHSN275201300023I-HHSN2750008. SL was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Main funding of the epigenetic studies in INMA was grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615, MS13/00054, CP18/00018), Generalitat de Catalunya-CIRIT 1999SGR 00241, Fundació La marató de TV3 (090430), EU Commission (261357-MeDALL: Mechanisms of the Development of ALLergy), and European Research Council (268479-BREATHE: BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn). The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; the Netherlands Organization for Health Research and Development; and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO), Netherlands Consortium for Healthy Aging (NCHA; project nr. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and by a grant from the National Institute of Child and Human Development (R01HD068437). This project received funding from the European Union's Horizon 2020 research and innovation programme (633595, DynaHEALTH: 733206, LIFECYCLE) and from the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022; and Precise project, ZonMw the Netherlands no. P75416). LD has received funding from the European Joint Programming Initiative. The PREDO study has been funded by the Academy of Finland, EraNet Neuron, EVO (a special state subsidy for health science research), University of Helsinki Research Funds, the Signe and Ane Gyllenberg Foundation, the Emil Aaltonen Foundation, the Finnish Medical Foundation, the Jane and Aatos Erkko Foundation, the Novo Nordisk Foundation, the Päivikki and Sakari Sohlberg Foundation, and the Sigrid Juselius Foundation granted to members of the PREDO study board. Methylation assays were funded by the Academy of Finland.

Background: studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. Objective: our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. Methods: we used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. Results: the prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. Conclusion: our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age ...

Background: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. Objective: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. Methods: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. Results: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. Conclusion: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age ...

Background: Prenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes. Objectives: We aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter <10 (PM10) or <2.5 mu m (PM2.5) and DNA methylation in newborns and children. Methods: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression. Results: Six CpGs were significantly associated [false discovery rate (FDR) <0.05] with prenatal PM10 and 14 with PM2.5 exposure. Two of the PM10-related CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant (p<0.05) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent PM10 exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal PM10 and or PM2.5 exposure, of which two PM10-related DMRs, including H19 and MARCH11, replicated in newborns. Conclusions: Several differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. ; ALSPAC: The UK Medical Research Council and the Wellcome Trust (Grant ref. 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and P.Y. will serve as guarantors for the contents of this paper. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristoLac.uk/alspac/external/documents/grant-acknowledgements.pdf). This research was specifically funded by a joint grant from the UK Economic & Social and Biotechnology & Biological Sciences Research Councils (Grant ref. ES/N000498/1). ALSPAC was funded by the BBSRC (BBI025751/1 and BB/I025263/1). Air pollution exposure assessment was funded by Public Health England as part of the MRC-PHE Centre for Environment and Health, funded also by the UK Medical Research Council (Grant ref. MR/L01341X/1). This paper does not necessarily reflect the views of Public Health England or the Department of Health. BAMSE was supported by The Swedish Research Council, The Swedish Heart-Lung Foundation, Freemason Child House Foundation in Stockholm, MeDALL (Mechanisms of the Development of ALLergy) a collaborative project conducted within the European Union (grant agreement No. 261357), Centre for Allergy Research, Stockholm County Council (ALE), Swedish Foundation for Strategic Research (SSF) (RBc08-0027), the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet, The Swedish Research Council Foams, and the Swedish Environment Protection Agency. E.M. is supported by a grant from the European Research Council under the European Union (EU) Horizon 2020 (H2020) research and innovation programme (grant agreement number 757919, TRIBAL). O.G. is supported by Forte (Swedish Research Council for Health, Working Life and Welfare) and The Swedish Society for Medical Research. CHS: This work was supported by NIEHS grants K01ES017801, R01ES022216, and P30ES007048. EARLI: This work was supported by NIH grants R01ES016443, R01ES023780, and R01ES017646 as well as by Autism Speaks (AS 5938). ENVIRONAGE: The ENVIRONAGE birth cohort is funded by the European Research Counsil (ERC-2012-StG.310898) and by funds of the Flemisch Scientific Research Council (FWO, N1516112/G.0.873.11N.10). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-Inserm, France) and Association pour la Recherche sur le Cancer (ARC, France). Generation R Study: The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center (MC), Rotterdam, the Erasmus University Rotterdam, Netherlands Organization for Health Research and Development and the Ministry of Health, Welfare and Sport. The EWAS data was funded by a grant to VWJ from Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA; project no. 050-060-810), by funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC. V.W.J. also received a grant from Netherlands Organization for Health Research and Development (VIDI 016.136.361) and a Consolidator Grant from the European Research Council (ERC-2014-CoG-648916). J.F.F. has received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement no. 633595 (DynaHEALTH). This project received funding from the European Union's Horizon 2020 Research and Innovation Programme (733206, LIFECYCLE). HELIX: The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-206) under grant agreement no 308333 - the HELIX project. R.G. received the grant of the Lithuanian Agency for Science Innovation and Technology (No. 45 31V-66). The Norwegian Mother and Child Cohort Study (MoBa) is supported by the Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no. N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). INMA: This study was funded by grants from Institut() de Salud Carlos III (Red INMA G03/176), Generalitat de Catalunya-CIRIT 1999SGR 00241, and EU Commission (261357; 211250; 268479). Piccolipiu: The study was approved and initially funded by the Italian National Centre for Disease Prevention and Control (CCM grant 2010) and by the Italian Ministry of Health (art 12 and 12bis Dl.gs.vo 502/92). The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (Grant agreement no: 308610). Z.H. and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA-INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). Rhea: The methylation assays were funded by the European Community's Seventh Framework Programme FP7/2007-2013 project EXPOsOMICS (grant no. 308610). Z.H. is supported by the Exposomics EC FP7 grant (grant agreement no. 308610). ZH and A.G. and the Epigenetics Group at IARC are supported by grants from the Institut National du Cancer (INCa, Plan Cancer-EVA INSERM, France) and Association pour la Recherche sur le Cancer (ARC, France). PRISM: R.J.W. received funding for the PRISM cohort under HL095606 and R01 HL1143396. A.C.J. is supported by R00 ES023450. Project Viva: This Project Viva study was supported by grants from the NIH (NIH R01 HL 111108, R01 NR013945, R01 HD 034568, K24 HD069408, K23 ES022242, P01ES009825, R01AI102960, P30 ES000002) and the U.S. Environmental Protection Agency (EPA) (R832416, RD834798). This publication's contents are solely the responsibility of the grantee and do not necessarily represent the official views of the U.S. Government, the U.S. Department of Health and Human Services or the NIH, or the EPA. Further, the EPA does not endorse the purchase of any commercial products or services mentioned in the publication. MeDALL: The methylation study of MeDALL cohorts was funded by MEDALL, a collaborative project supported by the European Union under the Health Cooperation Work Programme of the 7th Framework Programme (grant agreement no. 261357). The Biobank-Based Integrative Omics Studies (BIOS) Consortium is funded by BBMRI-NL, a research 'infrastructure financed by the Dutch government (NWO 184.021.007). BAMSE: We would like to thank all the families for their participation in the BAMSE study. In addition, we would like to thank E. Haliner, S. Nilsson, and A. Lauber at the BAMSE secretary for invaluable support, as well as Mutation Analysis Facility (MAF) at Karolinska Institutet for genome-wide methylation analysis, and I. Delin for excellent technical assistance. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) under Project b201.4110.