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1. Exposure to bushfire smoke is associated with clinical significant decrease in lung function in asthmatic children during the 2019/2020 Australian bushfire

Author

Da Silva Sena, C R, primary, Lines, O, additional, Latheef, M S, additional, Amarasinghe, G G, additional, Quah, W H, additional, Beyene, T, additional, Van Buskirk, J, additional, Hanigan, I, additional, Morgan, G, additional, Oldmeadow, C, additional, Platt, L, additional, Pearce, K, additional, Murphy, V, additional, Gibson, P G, additional, Karmaus, W, additional, Collison, A, additional, Dewaal, K, additional, and Mattes, J, additional

Published
2022
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4. The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study

Author

Hanjangsit K, Karmaus W, Dimitrov P, Zhang H, Burch J, Tzolova S, and Batuman V

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Kesinee Hanjangsit1, Wilfried Karmaus1, Plamen Dimitrov2, Hongmei Zhang1, Jim Burch1, Svetla Tzolova2, Vecihi Batuman3,41Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA; 2National Center of Public Health Protection, Sofia, Bulgaria; 3Section of Nephrology-Hypertension, Tulane University Medical Center, New Orleans, LA, USA; 4VA Medical Center, New Orleans, LA, USAAbstract: Balkan endemic nephropathy (BEN) is a chronic kidney disease that affects persons living in the Balkans. Despite the unique geographical specificity of this disease, its etiology has remained unclear. Even if a positive family history of BEN has been identified, it is still uncertain how the disease develops in offspring. In this paper, we examine clinical mechanisms related to the onset of BEN in individuals who have a parental history of BEN to identify early detection of the disease and formulate interventions. We conducted a 5-year prospective study, using markers in years one and three to predict new cases of BEN in year five. New cases of BEN were defined based on three criteria: parental history of BEN, reduced kidney size, and reduced kidney function. Incident cases were divided into (1) probable, (2) definite, and (3) combined labeled total incidence. We evaluated parental history in relation to BEN and tested the potentially intervening effects of kidney length, kidney cortex width, β2-microglobulin, C-reactive protein, and creatinine clearance, using path analyses. The findings of the path analyses suggested that parental history of BEN had both direct and indirect effects. The direct effect was significant for all three modes of parental history (biparental, maternal, and paternal; odds ratios 71.5, 52.3, and 50.1, respectively). The indirect effects of maternal BEN acted via kidney length and creatinine clearance. Biparental BEN was mediated by (1) kidney length and creatinine clearance, and (2) creatinine clearance alone. Paternal BEN had three indirect effects: (1) through kidney length and creatinine clearance, (2) via kidney cortex width and creatinine clearance, and (3) via kidney cortex width only. In conclusion, a family history of BEN led to reducedkidney length and cortex width, and a decline in creatinine clearance, which in turn predicted the onset of BEN.Keywords: Balkan endemic nephropathy, incidence of BEN, parental history of BEN, kidney size, β2-microglobulin, creatinine clearance

Published
2012

5. Adjusting wheal size measures to correct atopy misclassification

Author

Zhang H, Karmaus W, Gan J, Bao W, Zhao YD, Rahardja D, Holloway JW, Scott M, and Arshad SH.

Subjects
Medicine (General), R5-920
Abstract

Hongmei Zhang1,*, Wilfried Karmaus1,*, Jianjun Gan2, Weichao Bao1,*, Yan D Zhao3, Dewi Rahardja3, John W Holloway5, Martha Scott4,5, Syed Hasan Arshad4,51Department of Epidemiology and Biostatistics, The University of South Carolina, Columbia, SC, USA; 2GlaxoSmithKline, Research Triangle Park, NC, USA; 3Department of Clinical Science and Simmons Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA; 4The David Hide Asthma and Allergy Research Center, St Mary’s Hospital, Newport, Isle of Wight, UK; 5School of Medicine, University of Southampton, Southampton, UK *These authors contributed equally to this articlePurpose: Skin prick testing (SPT) is fundamental to the practice of clinical allergy identifying relevant allergens and predicting the clinical expression of disease. Wheal sizes on SPT are used to identify atopic cases, and the cut-off value for a positive test is commonly set at 3 mm. However, the measured wheal sizes do not solely reflect the magnitude of skin reaction to allergens, but also skin reactivity (reflected in the size of histamine reaction) and other random or non-random factors. We sought to estimate wheal sizes exclusively due to skin response to allergens and propose gender-specific cutoff points of atopy.Methods: We developed a Bayesian method to adjust observed wheal sizes by excluding histamine and other factor effects, based on which revised cutoff points are proposed for males and females, respectively. The method is then applied to and intensively evaluated using a study population aged 18, at a location on the Isle of Wight in the United Kingdom. To evaluate the proposed approach, two sample t-tests for population means and proportion tests are applied.Results: Four common aeroallergens, house dust mite (HDM), grass pollen, dog dander, and alternaria are considered in the study. Based on 3 mm cutoff, males tend to be more atopic than females (P-values are between 0.00087 and 0.062). After applying the proposed methods to adjust wheal sizes, our findings suggest that misclassifications of atopy occur more often in males. Revised allergen-specific cutoff values are proposed for each gender.Conclusion: To reduce the gender discrepancy, we may have two potentially convenient solutions. One way is to apply allergen-specific and gender-specific cutoff values following the proposed method. Alternatively, we can revise the concentration of allergens in the SPT solutions but keep the cutoff values unchanged, which may be more convenient to clinicians.Keywords: SPT, atopy, Bayesian method, joint modeling, misclassification

Published
2011

12. Cord blood group 2 innate lymphoid cells are associated with lung function at 6 weeks of age

Author

Martins Costa Gomes, G, de Gouveia Belinelo, P, Starkey, MR, Murphy, VE, Hansbro, PM, Sly, PD, Robinson, PD, Karmaus, W, Gibson, PG, Mattes, J, and Collison, AM

Subjects
1107 Immunology, 1115 Pharmacology and Pharmaceutical Sciences
Abstract

Objective: Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10-fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Methods: Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t-distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Results: Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty-four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor-homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age." Conclusion: Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life.

Published
2021

30. Hypertensive Disorders of Pregnancy and DNA Methylation in Newborns:Findings From the Pregnancy and Childhood Epigenetics Consortium

Author

Kazmi, N, Sharp, GC, Reese, SE, Vehmeijer, FO, Lahti, J, Page, CM, Zhang, WM, Rifas-Shiman, SL, Rezwan, FI, Simpkin, AJ, Burrows, K, Richardson, TG, Ferreira, D L S, Fraser, A, Harmon, QE, Zhao, SS, Jaddoe, Vincent, Czamara, D, Binder, EB, Magnus, MC, Haberg, SE, Nystad, W, Nohr, EA, Starling, AP, Kechris, KJ, Yang, IV, DeMeo, DL, Litonjua, AA, Baccarelli, A, Oken, E, Holloway, JW, Karmaus, W, Arshad, SH, Dabelea, D, Sorensen, TIA, Laivuori, H, Raikkonen, K, Felix, Janine, London, SJ, Hivert, MF, Gaunt, TR, Lawlor, DA, Relton, CL, Doctoral Programme in Cognition, Learning, Instruction and Communication, Department of Psychology and Logopedics, Developmental Psychology Research Group, Helsinki Collegium for Advanced Studies, University of Helsinki, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Pregnancy and Genes, University Management, Department of Medical and Clinical Genetics, Helsinki Institute of Life Science HiLIFE, Faculty of Medicine, Epidemiology, Erasmus MC other, and Pediatrics

Subjects
Adult, pre-eclampsia, hypertension, BIRTH, HYPOMETHYLATION, VASOPRESSIN, BLOOD-PRESSURE, Gestational Age, Epigenesis, Genetic, preeclampsia, Cohort Studies, Hypertension, Pregnancy-Induced/diagnosis, Pregnancy, gestational hypertension, Humans, COHORT, gestational age, METAANALYSIS, ASSOCIATIONS, DNA methylation, epigenetics, NORWEGIAN MOTHER, Infant, Newborn, Pregnancy Outcome, DNA, ALSPAC, Fetal Blood, cardiovascular diseases, 3121 General medicine, internal medicine and other clinical medicine, GENERATION R, FETAL-GROWTH, Female, methylation, DNA-Binding Proteins/genetics, Infant, Premature, Genome-Wide Association Study, DNA Methylation/genetics
Abstract

Hypertensive disorders of pregnancy (HDP) are associated with low birth weight, shorter gestational age, and increased risk of maternal and offspring cardiovascular diseases later in life. The mechanisms involved are poorly understood, but epigenetic regulation of gene expression may play a part. We performed meta-analyses in the Pregnancy and Childhood Epigenetics Consortium to test the association between either maternal HDP (10 cohorts; n=5242 [cases=476]) or preeclampsia (3 cohorts; n=2219 [cases=135]) and epigenome-wide DNA methylation in cord blood using the Illumina HumanMethylation450 BeadChip. In models adjusted for confounders, and with Bonferroni correction, HDP and preeclampsia were associated with DNA methylation at 43 and 26 CpG sites, respectively. HDP was associated with higher methylation at 27 (63%) of the 43 sites, and across all 43 sites, the mean absolute difference in methylation was between 0.6% and 2.6%. Epigenome-wide associations of HDP with offspring DNA methylation were modestly consistent with the equivalent epigenome-wide associations of preeclampsia with offspring DNA methylation (R-2=0.26). In longitudinal analyses conducted in 1 study (n=108 HDP cases; 550 controls), there were similar changes in DNA methylation in offspring of those with and without HDP up to adolescence. Pathway analysis suggested that genes located at/near HDP-associated sites may be involved in developmental, embryogenesis, or neurological pathways. HDP is associated with offspring DNA methylation with potential relevance to development.

Published
2019

31. Epigenome-wide meta-analysis of DNA methylation and childhood asthma

Author

Reese, S. E. (Sarah E.), Xu, C.-J. (Cheng-Jian), den Dekker, H. T. (Herman T.), Lee, M. K. (Mi Kyeong), Sikdar, S. (Sinjini), Ruiz-Arenas, C. (Carlos), Merid, S. K. (Simon K.), Rezwan, F. I. (Faisal I.), Page, C. M. (Christian M.), Ullemar, V. (Vilhelmina), Melton, P. E. (Phillip E.), Oh, S. S. (Sam S.), Yang, I. V. (Ivana V.), Burrows, K. (Kimberley), Söderhäll, C. (Cilla), Jima, D. D. (Dereje D.), Gao, L. (Lu), Arathimos, R. (Ryan), Küpers, L. K. (Leanne K.), Wielscher, M. (Matthias), Rzehak, P. (Peter), Lahti, J. (Jari), Laprise, C. (Catherine), Madore, A.-M. (Anne-Marie), Ward, J. (James), Bennett, B. D. (Brian D.), Wang, T. (Tianyuan), Bell, D. A. (Douglas A.), T. B. (The BIOS consortium), Vonk, J. M. (Judith M.), Håberg, S. E. (Siri E.), Zhao, S. (Shanshan), Karlsson, R. (Robert), Hollams, E. (Elysia), Hu, D. (Donglei), Richards, A. J. (Adam J.), Bergström, A. (Anna), Sharp, G. C. (Gemma C.), Felix, J. F. (Janine F.), Bustamante, M. (Mariona), Gruzieva, O. (Olena), Maguire, R. L. (Rachel L.), Gilliland, F. (Frank), Baïz, N. (Nour), Nohr, E. A. (Ellen A.), Corpeleijn, E. (Eva), Sebert, S. (Sylvain), Karmaus, W. (Wilfried), Grote, V. (Veit), Kajantie, E. (Eero), Magnus, M. C. (Maria C.), Örtqvist, A. K. (Anne K.), Eng, C. (Celeste), Liu, A. H. (Andrew H.), Kull, I. (Inger), Jaddoe, V. W. (Vincent W.V.), Sunyer, J. (Jordi), Kere, J. (Juha), Hoyo, C. (Cathrine), Annesi-Maesano, I. (Isabella), Arshad, S. H. (Syed Hasan), Koletzko, B. (Berthold), Brunekreef, B. (Bert), Binder, E. B. (Elisabeth B.), Räikkönen, K. (Katri), Reischl, E. (Eva), Holloway, J. W. (John W.), Järvelin, M.-R. (Marjo-Riitta), Snieder, H. (Harold), Kazmi, N. (Nabila), Breton, C. V. (Carrie V.), Murphy, S. K. (Susan K.), Pershagen, G. (Göran), Anto, J. M. (Josep Maria), Relton, C. L. (Caroline L.), Schwartz, D. A. (David A.), Burchard, E. G. (Esteban G.), Huang, R.-C. (Rae-Chi), Nystad, W. (Wenche), Almqvist, C. (Catarina), Henderson, A. J. (A. John), Melén, E. (Erik), Duijts, L. (Liesbeth), Koppelman, G. H. (Gerard H.), and London, S. J. (Stephanie J.)

Subjects
epigenetics, newborn, methylation, asthma, drug development, childhood
Abstract

Background: Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis. Objective: We sought to identify differential DNA methylation in newborns and children related to childhood asthma. Methods: Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions. Results: In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2. Conclusion: Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

Published
2019

44. Association of season of birth with DNA methylation and allergic disease

Author

Lockett, G. A., Soto-Ramirez, N., Ray, M. A., Everson, T. M., Xu, C-J., Patil, V. K., Terry, W., Kaushal, A., Rezwan, F. I., Ewart, S. L., Gehring, U., Postma, D. S., Koppelman, G. H., Arshad, S. H., Zhang, H., Karmaus, W., Holloway, J. W., LS IRAS EEPI ME (Milieu epidemiologie), Sub Medicinal Chemistry & Chemical biol., dIRAS RA-2, Groningen Research Institute for Asthma and COPD (GRIAC), LS IRAS EEPI ME (Milieu epidemiologie), Sub Medicinal Chemistry & Chemical biol., and dIRAS RA-2

Subjects
Male, 0301 basic medicine, Allergy, 0302 clinical medicine, Pregnancy, Immunology and Allergy, Child, RISK, DNA methylation, Methylation, epigenome-wide association study, 3. Good health, PREVALENCE, Maternal Exposure, Child, Preschool, Prenatal Exposure Delayed Effects, Cohort, INFANCY, Female, Disease Susceptibility, Seasons, 450K array, Cohort study, PACKAGE, Adolescent, Season of birth, DISORDERS, Immunology, Biology, Article, MECHANISMS, 03 medical and health sciences, Hypersensitivity, medicine, Humans, COHORT, Epigenetics, EARLY-CHILDHOOD, POLYMORPHISMS, epigenetics, season of birth, Infant, Newborn, Infant, Reproducibility of Results, Immunoglobulin E, medicine.disease, 030104 developmental biology, 030228 respiratory system, ASTHMA, CpG Islands
Abstract

BackgroundSeason of birth influences allergy risk; however, the biological mechanisms underlying this observation are unclear. The environment affects DNA methylation, with potentially long-lasting effects on gene expression and disease. This study examined whether DNA methylation could underlie the association between season of birth and allergy.MethodsIn a subset of 18-year-old participants from the Isle of Wight (IoW) birth cohort (n = 367), the risks of birth season on allergic outcomes were estimated. Whole blood epigenome-wide DNA methylation was measured, and season-associated CpGs detected using a training-and-testing-based technique. Validation method examined the 8-year-old Prevention and Incidence of Asthma and Mite Allergy (PIAMA) cohort. The relationships between DNA methylation, season of birth and allergy were examined. CpGs were analysed in IoW third-generation cohort newborns.ResultsAutumn birth increased risk of eczema, relative to spring birth. Methylation at 92 CpGs showed association with season of birth in the epigenome-wide association study. In validation, significantly more CpGs had the same directionality than expected by chance, and four were statistically significant. Season-associated methylation was enriched among networks relating to development, the cell cycle and apoptosis. Twenty CpGs were nominally associated with allergic outcomes. Two CpGs were marginally on the causal pathway to allergy. Season-associated methylation was largely absent in newborns, suggesting it arises post-natally.ConclusionsThis study demonstrates that DNA methylation in adulthood is associated with season of birth, supporting the hypothesis that DNA methylation could mechanistically underlie the effect of season of birth on allergy, although other mechanisms are also likely to be involved.

Published
2016

46. Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Author

Felix, JF, Joubert, BR, Baccarelli, AA, Sharp, GC, Almqvist, C, Annesi-Maesano, I, Arshad, H, Baïz, N, Bakermans-Kranenburg, MJ, Bakulski, KM, Binder, EB, Bouchard, L, Breton, CV, Brunekreef, B, Brunst, KJ, Burchard, EG, Bustamante, M, Chatzi, L, Munthe-Kaas, M, Corpeleijn, E, Czamara, D, Dabelea, D, Smith, G, De Boever, P, Duijts, L, Dwyer, T, Eng, C, Eskenazi, B, Everson, TM, Falahi, F, Fallin, MD, Farchi, S, Fernandez, MF, Gao, L, Gaunt, TR, Ghantous, A, Gillman, MW, Gonseth, S, Grote, V, Gruzieva, O, Håberg, SE, Herceg, Z, Hivert, M-F, Holland, N, Holloway, JW, Hoyo, C, Hu, D, Huang, R-C, Huen, K, Järvelin, M-R, Jima, DD, Just, AC, Karagas, MR, Karlsson, R, Karmaus, W, Kechris, KJ, Kere, J, Kogevinas, M, Koletzko, B, Koppelman, GH, Küpers, LK, Ladd-Acosta, C, Lahti, J, Lambrechts, N, Langie, SAS, Lie, RT, Liu, AH, Magnus, MC, Magnus, P, Maguire, RL, Marsit, CJ, McArdle, W, Melén, E, Melton, P, Murphy, SK, Nawrot, TS, Nisticò, L, Nohr, EA, Nordlund, B, Nystad, W, Oh, SS, Oken, E, Page, CM, Perron, P, Pershagen, G, Pizzi, C, Plusquin, M, Raikkonen, K, Reese, SE, Reischl, E, Richiardi, L, Ring, S, Roy, RP, Rzehak, P, Schoeters, G, Schwartz, DA, Sebert, S, Snieder, H, Sørensen, TIA, Starling, AP, Sunyer, J, Taylor, JA, Tiemeier, H, Ullemar, V, Vafeiadi, M, Van Ijzendoorn, MH, Vonk, JM, Vriens, A, Vrijheid, M, Wang, P, Wiemels, JL, Wilcox, AJ, Wright, RJ, Xu, C-J, Xu, Z, Yang, IV, Yousefi, P, Zhang, H, Zhang, W, Zhao, S, Agha, G, Relton, CL, Jaddoe, VWV, London, SJ, Epidemiology, Erasmus MC other, Pediatrics, Child and Adolescent Psychiatry / Psychology, Psychiatry, Research Methods and Techniques, dIRAS RA-2, One Health Chemisch, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Department of Psychology and Logopedics, Helsinki Collegium for Advanced Studies, Medicum, University of Helsinki, and Developmental Psychology Research Group

Subjects
DNA Methylation/physiology, Epidemiology, Maternal Health, education, Embaràs, DISEASE, Environmental Pollution/analysis, Epigenesis, Genetic, Cohort Studies, Prenatal Exposure Delayed Effects/epidemiology, Folic Acid, Pregnancy, Journal Article, Humans, MATERNAL SMOKING, CORD BLOOD, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Cohort Profiles, METAANALYSIS, PRENATAL EXPOSURE, Maternal Exposure/adverse effects, EPIGENOME-WIDE ASSOCIATION, 0104 Statistics, Child Health, Infant, Newborn, DNA METHYLATION DATA, DNA Methylation, Epigenètica, BIRTH-WEIGHT, 3142 Public health care science, environmental and occupational health, Folic Acid/blood, 1117 Public Health And Health Services, Maternal Exposure, Prenatal Exposure Delayed Effects, MENDELIAN RANDOMIZATION, Epigenetics, Female, Human medicine, Environmental Pollution
Abstract

UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); UK Medical Research Council; Wellcome Trust [102215/2/13/2, WT088806, 084762MA]; UK Biotechnology and Biological Sciences Research Council [BB/I025751/1, BB/I025263/1]; UK Medical Research Council Integrative Epidemiology Unit; University of Bristol [MC_UU_12013_1, MC_UU_12013_2, MC_UU_12013_5, MC_UU_12013_8]; United States National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK10324]; Swedish Research Council; Swedish Heart-Lung Foundation; Freemason Child House Foundation in Stockholm; MeDALL (Mechanisms of the Development of ALLergy), within the European Union [261357]; Stockholm County Council (ALF); Swedish Foundation for Strategic Research (SSF) [RBc08-0027]; Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet; Swedish Research Council Formas; Swedish Environment Protection Agency; Center for Integrative Research on Childhood Leukemia and the Environment [P01ES018172]; NIH [P50ES018172, R01ES09137, 5P30CA082103, P01 ES009605, R01 ES021369, R01ES023067, K01ES017801, R01ES022216, P30ES007048, R01ES014447, P01ES009581, R826708-01, RD831861-01, P50ES026086, R01DK068001, R01 DK100340, R01 DK076648, R01ES022934, R01HL111108, R01NR013945, R37 HD034568, UL1 TR001082, P30 DK56350]; EPA [RD83451101, RD83615901, RD 82670901, RD 83451301, 83615801-0]; UCSF Comprehensive Cancer Center Support grant [P30 CA82103]; Swiss Science National Foundation [P2LAP3_158674]; Sutter-Stottner Foundation; Commission of the European Community, specific RTD Programme 'Quality of Life and Management of Living Resources' within the 5th Framework Programme [QLRT-2001-00389, QLK1-CT-2002-30582]; 6th Framework Programme [007036]; European Union's Seventh Framework Programme (FP7), project EarlyNutrition [289346]; European Research Council Advanced grant ERC-AdG [322605 META-GROWTH]; Autism Speaks grant [260377]; Funds for Research in Respiratory Health; French Ministry of Research: IFR program; INSERM Nutrition Research Program; French Ministry of Health: Perinatality Program; French National Institute for Population Health Surveillance (INVS); Paris-Sud University; French National Institute for Health Education (INPES); Nestle; Mutuelle Generale de l'Education Nationale (MGEN); French-speaking association for the study of diabetes and metabolism (Alfediam) [2012/51290-6]; EU; European Research Council [ERC-2012-StG.310898, 268479-BREATHE]; Flemish Scientific Research Council (FWO) [N1516112 / G.0.873.11N.10]; European Community's Seventh Framework Programme FP7 project EXPOsOMICS [308610]; People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA grant [628858]; Bijzonder Onderzoeksfonds (BOF) Hasselt University; Ministry of the Flemish Community (Department of Economics, Science and Innovation); Ministry of the Flemish Community (Department of Environment, Nature and Energy); CEFIC LRI award by the Research Foundation-Flanders (FWO); CEFIC LRI award by the Research Foundation-Flanders (FWO) [12L5216N]; Flemish Institute for Technological Research (VITO) [12L5216N]; Bill AMP; Melinda Gates Foundation Grand Challenges Exploration grant [OPP119403]; Sandler Family Foundation; American Asthma Foundation; National Institutes of Health; National Heart, Lung and Blood Institute [HL117004]; National Institute of Environmental Health Sciences [ES24844]; National Institute on Minority Health and Health Disparities [MD006902, MD009523]; National Institute of General Medical Sciences [GM007546]; Tobacco-Related Disease Research Program [24RT-0025]; Hutchison Whampoa Ltd, Hong Kong; University of Groningen; Well Baby Clinic Foundation Icare; Noordlease; Youth Health Care Drenthe; Biobanking and Biomolecular Research Infrastructure Netherlands [CP2011-19]; Erasmus Medical Center, Rotterdam; Erasmus University Rotterdam; Netherlands Organization for Health Research and Development; Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO); Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]; Genetic Laboratory of the Department of Internal Medicine, Erasmus MC; European Union's Horizon research and innovation programme [733206, 633595]; National Institute of Child and Human Development [R01HD068437]; Netherlands Organization for Health Research and Development [VIDI 016.136.361]; Consolidator grant from the European Research Council [ERC-2014-CoG-648916]; Netherlands' Organization for Scientific Research (NWO VICI); European Research Council ERC; Netherlands' Organization for Scientific Research (NWO Spinoza Award); Gravitation program of the Dutch Ministry of Education, Culture, and Science; Netherlands Organization for Scientific Research (NWO) [024.001.003]; Lung Foundation Netherlands [3.2.12.089]; Fonds de Recherche du Quebec en Sante (FRQ-S) [20697]; Canadian Institute of Health Reseach (CIHR) [MOP 115071]; Diabete Quebec grant; Canadian Diabetes Association operating grant [OG-3-08-2622]; American Diabetes Association Pathways Accelerator Early Investigator Award [1-15-ACE-26]; MRC Integrative Epidemiology Unit - Medical Research Council [MC_UU_12013/1-9]; National Institute of Environmental Health Sciences, National Institutes of Health [K99ES025817]; Instituto de Salud Carlos III [Red INMA G03/176, CB06/02/0041]; Spanish Ministry of Health [FIS-PI04/1436, FIS-PI08/1151]; Spanish Ministry of Health (FEDER funds) [FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615]; Generalitat de Catalunya [CIRIT 1999SGR 00241]; Fundacio La Marato de TV3 [090430]; EU Commission [261357-MeDALL]; National Institute of Allergy and Infectious Diseases [N01-AI90052]; National Institutes of Health USA [R01 HL082925, R01 HL132321]; Asthma UK [364]; NIAID/NIH [R01AI091905, R01AI121226]; National Institute of Health [R01AI121226, R01 AI091905, R01HL132321]; NIH/NIEHS [N01-ES75558]; NIH/NINDS [1 UO1 NS 047537-01, 2 UO1 NS 047537-06A1]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01-ES-49019, Z01 ES044005, ES049033, ES049032]; Norwegian Research Council/BIOBANK [221097]; Oslo University Hospital; Unger-Vetlesens foundation; Norwegian American Womens Club; INCA/Plan Cancer-EVA-INSERM, France; International Childhood Cancer Cohort Consortium (I4C); INCA/Plan Cancer-EVA-INSERM (France); IARC Postdoctoral Fellowship; EC FP7 Marie Curie Actions-People-Co-funding of regional, national and international programmes (COFUND); NIEHS [R21ES014947, R01ES016772]; NIDDK [R01DK085173]; National Institute of Environmental Health Science [P30 ES025128]; University of Oulu grant [65354]; Oulu University Hospital [2/97, 8/97]; Ministry of Health and Social Affairs [23/251/97, 160/97, 190/97]; National Institute for Health and Welfare, Helsinki [54121]; Regional Institute of Occupational Health, Oulu, Finland [50621, 54231]; EU [QLG1-CT-2000-01643, E51560]; NorFA grant [731, 20056, 30167]; Academy of Finland; NIH-NIEHS [P01 ES022832]; US EPA [RD83544201]; NIH-NIGMS [P20GM104416]; NCI [R25CA134286]; Netherlands Organization for Scientific Research and Development; Netherlands Asthma Fund; Netherlands Ministry of Spatial Planning, Housing, and the Environment; Netherlands Ministry of Health, Welfare, and Sport; MeDALL; European Union under the Health Cooperation Work Program of the 7th Framework program [261357]; Italian National Centre for Disease Prevention and Control (CCM grant); Italian Ministry of Health (art 12); Italian Ministry of Health (12bis Dl.gs.vo) [502/92]; EraNet; EVO; University of Helsinki Research Funds; Signe and Ane Gyllenberg foundation; Emil Aaltonen Foundation; Finnish Medical Foundation; Jane and Aatos Erkko Foundation; Novo Nordisk Foundation; Paivikki and Sakari Sohlberg Foundation; Sigrid Juselius Foundation; University of Helsinki; University of Western Australia (UWA); Curtin University; Raine Medical Research Foundation; UWA Faculty of Medicine, Dentistry and Health Sciences; Telethon Kids Institute; Women's and Infant's Research Foundation (KEMH); Edith Cowan University; National Health and Medical Research Council [1059711]; National Health and Medical Research Council (NHMRC) fellowship [1053384]; Australian National Health and Medical Research Council; United States National Institute of Health; Greek Ministry of Health (programme of prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece); Greek Ministry of Health ('Rhea Plus': Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health); European Union (EU) [EU FP6-2003-Food-3-NewGeneris, EU FP7 ENV.2007.1.2.2.2, 211250 ESCAPE, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7 ENV.2008.1.2.1.6, 226285 ENRIECO]; National Institutes of Health [NIH-NIMH R01MH094609, NIH-NIEHS R01ES022223, NIH-NIEHS R01ES025145]; Centers for Disease Control and Prevention [U10DD000180, U10DD000181, U10DD000182, U10DD000183, U10DD000184, U10DD000498]; Autism Speaks [7659]; Swedish Research Council through the Swedish Initiative for research on Microdata in the Social And Medical Sciences (SIMSAM) [340-2013-5867]; Stockholm County Council (ALF projects); Strategic Research Program in Epidemiology at Karolinska Institutet; Swedish Asthma and Allergy Association's Research Foundation; Stiftelsen Frimurare Barnahuset Stockholm; Norwegian Ministry of Health and Care Services; Ministry of the Flemish Community (Flemish Agency for Care and Health); University of Bristol; Ministry of Education and Research; European Union (EU) (EU FP7-HEALTH-single stage CHICOS); European Union (EU) (EU-FP7-HEALTH) [308333 HELIX]; European Union (EU) (EU FP6. STREP HiWATE); [R01ES017646]; [R01ES01900]; [R01ES16443]; [USA / NIHH 2000 G DF682]; [50945]; [R01 HL095606]; [R01 HL1143396]

Published
2018

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