DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication

Serdarevic, Fadila; Luo, Mannan; Karabegović, Irma; Binter, Anne-Claire; Alemany, Silvia; Mutzel, Ryan; Guxens Junyent, Mònica; Bustamante Pineda, Mariona; Hajdarpasic, Aida; White, Tonya; Felix, Janine Frédérique; Cecil, Charlotte A. M.; Tiemeier, Henning

DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication

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dc.contributor.author Serdarevic, Fadila
dc.contributor.author Luo, Mannan
dc.contributor.author Karabegović, Irma
dc.contributor.author Binter, Anne-Claire
dc.contributor.author Alemany, Silvia
dc.contributor.author Mutzel, Ryan
dc.contributor.author Guxens Junyent, Mònica
dc.contributor.author Bustamante Pineda, Mariona
dc.contributor.author Hajdarpasic, Aida
dc.contributor.author White, Tonya
dc.contributor.author Felix, Janine Frédérique
dc.contributor.author Cecil, Charlotte A. M.
dc.contributor.author Tiemeier, Henning
dc.date.accessioned 2023-07-04T06:42:25Z
dc.date.available 2023-07-04T06:42:25Z
dc.date.issued 2023
dc.description.abstract Lower fine motor performance in childhood has been associated with poorer cognitive development and neurodevelopmental conditions such as autism spectrum disorder, yet, biological underpinnings remain unclear. DNA methylation (DNAm), an essential process for healthy neurodevelopment, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm with childhood fine motor ability and further examined the replicability of epigenetic markers in an independent cohort. The discovery study was embedded in Generation R, a large population-based prospective cohort, including a subsample of 924 ~ 1026 European-ancestry singletons with available data on DNAm in cord blood and fine motor ability at a mean (SD) age of 9.8 (0.4) years. Fine motor ability was measured using a finger-tapping test (3 subtests including left-, right-hand and bimanual), one of the most frequently used neuropsychological instruments of fine motor function. The replication study comprised 326 children with a mean (SD) age of 6.8 (0.4) years from an independent cohort, the INfancia Medio Ambiente (INMA) study. Four CpG sites at birth were prospectively associated with childhood fine motor ability after genome-wide correction. Of these, one CpG (cg07783800 in GNG4) was replicated in INMA, showing that lower levels of methylation at this site were associated with lower fine motor performance in both cohorts. GNG4 is highly expressed in the brain and has been implicated in cognitive decline. Our findings support a prospective, reproducible association between DNAm at birth and fine motor ability in childhood, pointing to GNG4 methylation at birth as a potential biomarker of fine motor ability.
dc.description.sponsorship 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), funds from the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, and a grant from the National Institute of Child and Human Development (R01HD068437). HT was 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). FS was supported by a Royal Netherlands Academy of Science and Art (KNAW) Van Leersum fellowship. ML is supported by the scholarship from the China Scholarship Council (201706990036). CC is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements No 101039672 (TEMPO) and No 848158 (EarlyCause). This project received funding from the European Union’s Horizon 2020 research and innovation programme (733206, LifeCycle).The epigenetic studies in INMA were mainly funded by grants from Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, CP18/00018), Spanish Ministry of Health (FIS-PI04/1436, FIS-PI08/1151 including FEDER funds, FIS-PI11/00610, FIS-FEDER-PI06/0867, FIS-FEDER-PI03-1615) 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).
dc.format.mimetype application/pdf
dc.identifier.citation Serdarevic F, Luo M, Karabegović I, Binter AC, Alemany S, Mutzel R, Guxens M, Bustamante M, Hajdarpasic A, White T, Felix JF, Cecil CAM, Tiemeier H. DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication. Epigenetics. 2023;18(1):2207253. DOI: 10.1080/15592294.2023.2207253
dc.identifier.doi http://dx.doi.org/10.1080/15592294.2023.2207253
dc.identifier.issn 1559-2294
dc.identifier.uri http://hdl.handle.net/10230/57452
dc.language.iso eng
dc.publisher Taylor & Francis
dc.relation.ispartof Epigenetics. 2023;18(1):2207253
dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101039672
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848158
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/261357
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/268479
dc.rights © 2023 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.keyword DNA methylation
dc.subject.keyword EWAS
dc.subject.keyword Cognitive function
dc.subject.keyword Cord blood
dc.subject.keyword Fine motor development
dc.title DNA methylation at birth and fine motor ability in childhood: an epigenome-wide association study with replication
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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