DNA methylation and general psychopathology in childhood : an epigenome-wide meta-analysis from the PACE consortium
Rijlaarsdam, Jolien (Erasmus MC University Medical Center Rotterdam)
Cosin-Tomas, Marta (Universitat Pompeu Fabra)
Schellhas, Laura (University Medical Center Hamburg)
Abrishamcar, Sarina (Emory University)
Malmberg, Anni (University of Helsinki)
Neumann, Alexander (VIB Center for Molecular Neurology)
Felix, Janine F. (Erasmus MC University Medical Center Rotterdam)
Sunyer, Jordi (Centro de investigación biomédica en red en epidemiología y salud pública (ciberesp))
Gutzkow, Kristine B. (Norwegian Institute of Public Health (NIPH))
Grazuleviciene, Regina (Vytautas Magnus University)
Wright, John (Bradford Teaching Hospitals NHS Foundation Trust)
Kampouri, Mariza (University of Crete)
Zar, Heahter J (University of Cape Town)
Stein, Dan J. (University of Cape Town)
Heinonen, Kati (University of Helsinki)
Räikkönen, Katri (University of Helsinki)
Lahti, Jari (University of Helsinki)
Hüls, Anke (Emory University)
Caramaschi, Doretta (University of Exeter)
Alemany, Sílvia (Hospital Universitari Vall d'Hebron)
Cecil, Charlotte A. M. (Leiden University Medical Center)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	The general psychopathology factor (GPF) has been proposed as a way to capture variance shared between psychiatric symptoms. Despite a growing body of evidence showing both genetic and environmental influences on GPF, the biological mechanisms underlying these influences remain unclear. In the current study, we conducted epigenome-wide meta-analyses to identify both probe- and region-level associations of DNA methylation (DNAm) with school-age general psychopathology in six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. DNAm was examined both at birth (cord blood; prospective analysis) and during school-age (peripheral whole blood; cross-sectional analysis) in total samples of N = 2178 and N = 2190, respectively. At school-age, we identified one probe (cg11945228) located in the Bromodomain-containing protein 2 gene (BRD2) that negatively associated with GPF (p = 8. 58 × 10 -8). We also identified a significant differentially methylated region (DMR) at school-age (p = 1. 63 × 10 -8), implicating the SHC Adaptor Protein 4 (SHC4) gene and the EP300-interacting inhibitor of differentiation 1 (EID1) gene that have been previously implicated in multiple types of psychiatric disorders in adulthood, including obsessive compulsive disorder, schizophrenia, and major depressive disorder. In contrast, no prospective associations were identified with DNAm at birth. Taken together, results of this study revealed some evidence of an association between DNAm at school-age and GPF. Future research with larger samples is needed to further assess DNAm variation associated with GPF.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biomarkers ; Genetics
Published in:	Molecular psychiatry, Vol. 28 (november 2022) , p. 1128-1136, ISSN 1476-5578

DOI: 10.1038/s41380-022-01871-6
PMID: 36385171

0 p, 773.7 KB

The record appears in these collections:
Articles > Research articles
Articles > Published articles