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

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Neumann, Alexander
  • dc.contributor.author Alemany, Silvia
  • dc.contributor.author González, Juan Ramón
  • dc.contributor.author Julvez, Jordi
  • dc.contributor.author Maitre, Léa
  • dc.contributor.author Sunyer Deu, Jordi
  • dc.contributor.author Guxens Junyent, Mònica
  • dc.contributor.author Tiemeier, Henning
  • dc.date.accessioned 2022-06-07T05:53:57Z
  • dc.date.available 2022-06-07T05:53:57Z
  • dc.date.issued 2020
  • dc.description.abstract 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 unknown. 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 both DNA methylation in cord blood with repeatedly assessed ADHD symptoms (age 4-15 years) in 2477 children from 5 cohorts and of DNA methylation at school age with concurrent ADHD symptoms (age 7-11 years) in 2374 children from 9 cohorts, with 3 cohorts participating at both timepoints. CpGs identified with nominal significance (p < 0.05) in either of the EWAS were correlated between timepoints (ρ = 0.30), suggesting overlap in associations; however, top signals were very different. At birth, we identified nine CpGs that predicted later ADHD symptoms (p < 1 × 10-7), including ERC2 and CREB5. Peripheral blood DNA methylation at one of these CpGs (cg01271805 in the promoter region of ERC2, which regulates neurotransmitter release) was previously associated with brain methylation. Another (cg25520701) lies within the gene body of CREB5, which previously was associated with neurite outgrowth and an ADHD diagnosis. In contrast, at school age, no CpGs were associated with ADHD with p < 1 × 10-7. In conclusion, we found evidence in this study that 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.
  • dc.description.sponsorship We gratefully acknowledge the contribution of general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The generation and management of the Illumina 450K methylation array data (EWAS data) for the Generation R Study was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Netherlands. We thank Mr. Michael Verbiest, Ms. Mila Jhamai, Ms. Sarah Higgins, Mr. Marijn Verkerk, and Dr. Lisette Stolk for their help in creating the EWAS database. We thank Dr. A. Teumer for his work on the quality control and normalization scripts. The general design of the Generation R Study is made possible by financial support from Erasmus Medical Center, Rotterdam, Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), and the Ministry of Health, Welfare and Sport. The EWAS data were 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). A.N. and H.T. are supported by a grant of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant No. 024.001.003, Consortium on Individual Development). A.N. is also supported by a Canadian Institutes of Health Research team grant. The work of H.T. is further supported by a NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200). M.v.I. and M.B.-K. were supported by the Netherlands Organization for Scientific Research (SPINOZA, VICI), and M.B.-K. was supported by the European Research Council (AdG 669249). J.F.F. has received funding from the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL, NutriPROGRAM project, ZonMw the Netherlands no.529051022). This project received funding from the European Union’s Horizon 2020 research and innovation program (733206, LifeCycle; 633595, DynaHEALTH).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Neumann A, Walton E, Alemany S, Cecil C, González JR, Jima DD et al. Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis. Transl Psychiatry. 2020 Nov 12;10(1):398. DOI: 10.1038/s41398-020-01058-z
  • dc.identifier.doi http://dx.doi.org/10.1038/s41398-020-01058-z
  • dc.identifier.issn 2158-3188
  • dc.identifier.uri http://hdl.handle.net/10230/53390
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Transl Psychiatry. 2020 Nov 12;10(1):398
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/633595
  • dc.rights © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Genetics
  • dc.subject.keyword Psychiatric disorders
  • dc.title Association between DNA methylation and ADHD symptoms from birth to school age: a prospective meta-analysis
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

Col·leccions

Articles (Barcelona Institute for Global Health (ISGlobal) – Campus Mar)
Articles (Departament de Medicina i Ciències de la Vida)
Documents OpenAIRE (Open Access Infrastructure for Research in Europe)