Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Felix, Janine F.; Joubert, Bonnie R.; Baccarelli, Andrea A.; Sharp, Gemma C; Almqvist, Catarina; Annesi‐Maesano, Isabella; Arshad, Hasan; Baïz, Nour; Bakermans‐Kranenburg, Marian J.; Bakulski, Kelly M.; Binder, Elisabeth B.; Bouchard, Luigi; Breton, Carrie V.; Brunekreef, Bert; Brunst, Kelly J.; Burchard, Esteban G.; Bustamante, Mariona; Chatzi, Leda; Munthe‐Kaas, Monica Cheng; Corpeleijn, Eva; Czamara, Darina; Dabelea, Dana; Smith, George Davey; Boever, Patrick De; Duijts, Liesbeth; Dwyer, Terence; Eng, Celeste; Eskenazi, Brenda; Everson, Todd M.; Falahi, Fahimeh; Fallin, M. Daniele; Farchi, Sara; Fernández, Mariana F.; Gao, Lu; Gaunt, Tom R.; Ghantous, Akram; Gillman, Matthew W.; Gonseth, Semira; Grote, Veit; Gruzieva, Olena; Håberg, Siri E.; Herceg, Zdenko; Hivert, Marie‐France; Holland, Nina; Holloway, John W.; Hoyo, Cathrine; Hu, Donglei; Huang, Rae‐Chi; Huen, Karen; Järvelin, Marjo‐Riitta; Jima, Dereje D.; Just, Allan C.; Karagas, Margaret R.; Karlsson, Robert; Karmaus, Wilfried; Kechris, Katerina; Kere, Juha; Kogevinas, Manolis; Koletzko, Berthold; Koppelman, Gerard H.; Küpers, Leanne K.; Ladd‐Acosta, Christine; Lahti, Jari; Lambrechts, Nathalie; Langie, Sabine A. S.; Lie, Rolv Terje; Liu, Andrew H.; Magnus, Maria C; Magnus, Per; Maguire, Rachel; Marsit, Carmen J.; McArdle, Wendy L.; Melén, Erik; Melton, Phillip E.; Murphy, Susan K.; Nawrot, Tim S.; Nisticò, Lorenza; Nøhr, Ellen Aagaard; Nordlund, Björn; Nystad, Wenche; Oh, Sam S.; Oken, Emily; Page, Christian M.; Perron, Patrice; Pershagen, Göran; Pizzi, Costanza; Plusquin, Michelle; Räikkönen, Katri; Reese, Sarah E.; Reischl, Eva; Richiardi, Lorenzo; Ring, Susan M.; Roy, Ritu; Rzehak, Peter; Schoeters, Greet; Schwartz, David A.; Sebért, Sylvain; Snieder, Harold; Sørensen, Thorkild I A; Starling, Anne P.; Sunyer, Jordi; Taylor, Jack A.; Tiemeier, Henning; Ullemar, Vilhelmina; Vafeiadi, Marina; IJzendoorn, M.H. van; Vonk, Judith M.; Vriens, Annette; Vrijheid, Martine; Wang, Pei; Wiemels, Joseph L.; Wilcox, Allen J.; Wright, Rosalind J.; Xu, Cheng‐Jian; Xu, Zongli; Yang, Ivana V.; Yousefi, Paul; Zhang, Hongmei; Zhang, Weiming; Zhao, Shanshan; Agha, Golareh; Relton, Caroline L; Jaddoe, Vincent W.V.; London, Stephanie J.

doi:10.1093/ije/dyx190

Cited by 114 publications

(88 citation statements)

References 62 publications

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“…We examined DNA methylation levels in newborns in relation to gestational age in a large-scale meta-analysis and also examined functional effects on expression of nearby genes of potential relevance for later health. We meta-analysed harmonized cohort specific EWAS results of the association of gestational age with cord blood DNA methylation levels from the Pregnancy And Childhood Epigenetics (PACE) Consortium of pregnancy and childhood cohorts [31]. We also examined associations with continuous gestational age limited to term newborns.…”

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

et al. 2020

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“…Consortiums such as Pregnancy and Childhood Epigenetics (PACE) currently pool 450K data for large-scale EWAS meta-analyses [2]; however, many participating cohorts are now obtaining EPIC data. With the shift to the EPIC platform, a critical question is whether individual cohort studies or meta-analyses can make use of data from both platforms.…”

Section: Introductionmentioning

confidence: 99%

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

et al. 2018

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Analysis of DNA methylation helps to understand the effects of environmental exposures as well as the role of epigenetics in human health. Illumina, Inc. recently replaced the HumanMethylation450 BeadChip (450K) with the EPIC BeadChip, which nearly doubles the measured CpG sites to >850,000. Although the new chip uses the same underlying technology, it is important to establish if data between the two platforms are comparable within cohorts and for meta-analyses. DNA methylation was assessed by 450K and EPIC using whole blood from newborn (n = 109) and 14-year-old (n = 86) participants of the Center for the Health Assessment of Mothers and Children of Salinas. The overall per-sample correlations were very high (r >0.99), although many individual CpG sites, especially those with low variance of methylation, had lower correlations (median r = 0.24). There was also a small subset of CpGs with large mean methylation β-value differences between platforms, in both the newborn and 14-year datasets. However, estimates of cell type proportion prediction by 450K and EPIC were highly correlated at both ages. Finally, differentially methylated positions between boys and girls replicated very well by both platforms in newborns and older children. These findings are encouraging for application of combined data from EPIC and 450K platforms for birth cohorts and other population studies. These data in children corroborate recent comparisons of the two BeadChips in adults and in cancer cell lines. However, researchers should be cautious when characterizing individual CpG sites and consider independent methods for validation of significant hits.

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“…18 While considerable research has begun to investigate DNA methylation in relation to ADHD, large multi-center epigenome-wide studies, which allow for increased power and generalizability, are lacking in childhood. Here we performed the first epigenome-wide prospective meta-analysis to identify DNA methylation sites associated with childhood ADHD symptoms employing cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium 19 . Since the temporal stability of methylation potentially associated with ADHD symptoms is unclear, we tested DNA methylation both at birth using cord blood and in school-age (age 7-9 years) using DNA derived from peripheral whole blood.…”

Section: Introductionmentioning

confidence: 99%

Association between DNA methylation and ADHD symptoms from birth to school age: A prospective meta-analysis

Neumann

Walton

Alemany

et al. 2019

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Attention-deficit and hyperactivity disorder (ADHD) is a common childhood disorder with a substantial genetic component. However, the extent to which epigenetic mechanisms play a role in the etiology of the disorder is not known. We performed epigenome-wide association studies (EWAS) within the Pregnancy And Childhood Epigenetics (PACE) Consortium to identify DNA methylation sites associated with ADHD symptoms at two methylation assessment periods: birth and school-age. We examined associations of DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age range 4-15 years) in 2477 children from five cohorts and DNA methylation at school-age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from ten cohorts. The regression estimates at nominal significance of the two EWAS (birth and school-age methylation) correlated (ρ=0.30) between both time points. At birth, we identified nine probes that were associated with later ADHD symptoms at genome-wide significance, including ERC2 and CREB5. Peripheral blood DNA methylation at one of these probes (cg01271805 located in the promotor region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another genome-wide significant probe (cg25520701) lies within the gene body of CREB5, which was associated with neurite outgrowth and an ADHD diagnosis in previous studies. In contrast, no probes reached genome-wide significance when ADHD was associated with school-age DNA methylation. In conclusion, DNA methylation at birth is associated with ADHD. Future studies are needed to confirm the utility of methylation variation as biomarker and its involvement in causal pathways.

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Cohort Profile: Pregnancy And Childhood Epigenetics (PACE) Consortium

Cited by 114 publications

References 62 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

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

Association between DNA methylation and ADHD symptoms from birth to school age: A prospective meta-analysis

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