DNA methylation and general psychopathology in childhood: an epigenome-wide meta-analysis from the PACE consortium.
Jolien RijlaarsdamMarta Cosin-TomasLaura SchellhasSarina AbrishamcarAnni MalmbergAlexander NeumannJanine F FelixJordi SunyerKristine B GutzkowRegina GrazulevicieneJohn WrightMariza KampouriHeather J ZarDan J SteinKati HeinonenKatri RäikkönenJari M T LahtiAnke HülsDoretta CaramaschiSilvia AlemanyCharlotte A M CecilPublished in: Molecular psychiatry (2022)
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.
Keyphrases
- dna methylation
- genome wide
- major depressive disorder
- meta analyses
- copy number
- systematic review
- obsessive compulsive disorder
- cord blood
- nk cells
- bipolar disorder
- gene expression
- cross sectional
- depressive symptoms
- genome wide identification
- pregnancy outcomes
- magnetic resonance
- early life
- randomized controlled trial
- amino acid
- anorexia nervosa
- living cells
- physical activity
- deep brain stimulation
- preterm birth
- protein kinase
- quantum dots
- transcription factor
- climate change
- single molecule
- data analysis