DNA methylation and general psychopathology in childhood: an epigenome-wide meta-analysis from the PACE consortium

Jolien Rijlaarsdam, Marta Cosin-Tomas*, Laura Schellhas, Sarina Abrishamcar, Anni Malmberg, Alexander Neumann, Janine F. Felix, Jordi Sunyer, Kristine B. Gutzkow, Regina Grazuleviciene, John Wright, Mariza Kampouri, Heather J. Zar, Dan J. Stein, Kati Heinonen, Katri Räikkönen, Jari Lahti, Anke Hüls, Doretta Caramaschi, Silvia AlemanyCharlotte A.M. Cecil*

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)1128-1136
Number of pages9
JournalMolecular Psychiatry
Issue number3
Publication statusPublished - Mar 2023

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© 2022, The Author(s), under exclusive licence to Springer Nature Limited.


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