Academic Journal
Genetic Susceptibility to Neurodevelopmental Conditions Is Associated With Neonatal DNA Methylation Patterns in the General Population: An Individual Participant Data Meta-Analysis.
| Τίτλος: | Genetic Susceptibility to Neurodevelopmental Conditions Is Associated With Neonatal DNA Methylation Patterns in the General Population: An Individual Participant Data Meta-Analysis. |
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| Συγγραφείς: | Schuurmans IK; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands., Smajlagic D; PROMENTA Research Centre, Department of Psychology, University of Oslo, Oslo, Norway., Baltramonaityte V; Department of Psychology, University of Bath, Bath, United Kingdom., Malmberg ALK; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Neumann A; Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands., Creasey N; Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Division of Psychology & Language Sciences, Department of Clinical, Educational, and Health Psychology, University College London, London, United Kingdom., Felix JF; Generation R Study Group, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Pediatrics, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands., Tiemeier H; Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Social and Behavioral Sciences, Harvard TH Chan School of Public Health, Boston, Massachusetts., Pingault JB; Division of Psychology & Language Sciences, Department of Clinical, Educational, and Health Psychology, University College London, London, United Kingdom; Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom., Czamara D; Department Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany., Raïkkönen K; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Page CM; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway., Lyle R; Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., Havdahl A; PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo, Norway., Lahti J; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Walton E; Department of Psychology, University of Bath, Bath, United Kingdom., Bekkhus M; PROMENTA Research Centre, Department of Psychology, University of Oslo, Oslo, Norway., Cecil CAM; Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry and Psychology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: c.cecil@erasmusmc.nl. |
| Πηγή: | Biological psychiatry [Biol Psychiatry] 2026 Aug 15; Vol. 100 (4), pp. 414-425. Date of Electronic Publication: 2025 Sep 22. |
| Τύπος έκδοσης: | Journal Article; Meta-Analysis |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE |
| Imprint Name(s): | Publication: New York, NY : Elsevier Original Publication: New York, Plenum Pub. Corp. |
| Ιατρικοί όροι (MeSH): | DNA Methylation*/genetics , Schizophrenia*/genetics , Autism Spectrum Disorder*/genetics , Attention Deficit Disorder with Hyperactivity*/genetics , Neurodevelopmental Disorders*/genetics , Genetic Predisposition to Disease*, Humans ; Female ; Genetic Risk Score ; Infant, Newborn ; Male ; Child ; Adolescent ; Child, Preschool ; Epigenesis, Genetic ; Fetal Blood ; Infant |
| Περίληψη: | Background: Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in fetal neurodevelopment. Epigenetic processes, such as DNA methylation (DNAm), are considered a key pathway of interest. However, it is unclear whether 1) genetic susceptibility to neurodevelopmental conditions (NDCs) is associated with DNAm patterns already at birth, 2) DNAm patterns are unique or shared across conditions, and 3) neonatal DNAm patterns can be leveraged to enhance genetic prediction of neurodevelopmental outcomes. Methods: We conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and SCZ (measured with polygenic scores [PGSs]) and cord blood DNAm in 4 European population-based cohorts (n Results: In probe-level analyses, the SCZ PGS was associated with neonatal DNAm at 246 loci (p < 9 × 10-8), predominantly in the major histocompatibility complex, supporting an early-origins perspective on SCZ. Functional characterization confirmed strong genetic effects, blood-brain concordance, and enrichment for immune-related pathways. Eight loci were identified for the ASD PGS (mapping to FDFT1 and MFHAS1) and none for the ADHD PGS. Differentially methylated regions were detected across PGSs (130-166 regions). Overall, DNAm signals were largely distinct between conditions. Incorporating neonatal DNAm data in genetic prediction models nominally increased the explained variance for several cognitive and motor outcomes. Conclusions: Genetic susceptibility to NDCs, particularly SCZ, is detectable in cord blood DNAm in the general population. (Copyright © 2025 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.) |
| Σχόλια: | Update of: medRxiv. 2024 Jul 01:2024.07.01.24309384. doi: 10.1101/2024.07.01.24309384.. (PMID: 39006433) |
| Contributed Indexing: | Keywords: DNA methylation; Epigenetics; Genetic susceptibility; Neurodevelopmental conditions; Population-based; Schizophrenia |
| Entry Date(s): | Date Created: 20250924 Date Completed: 20260722 Latest Revision: 20260722 |
| Update Code: | 20260723 |
| DOI: | 10.1016/j.biopsych.2025.09.005 |
| PMID: | 40992585 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-2402 |
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| DOI: | 10.1016/j.biopsych.2025.09.005 |