Neonatal DNA methylation and childhood low prosocial behavior: An epigenome‐wide association meta‐analysis

Abstract

Low prosocial behavior in childhood has been consistently linked to later psychopathology, with evidence supporting the influence of both genetic and environmental factors on its development. Although neonatal DNA methylation (DNAm) has been found to prospectively associate with a range of psychological traits in childhood, its potential role in prosocial development has yet to be investigated. This study investigated prospective associations between cord blood DNAm at birth and low prosocial behavior within and across four longitudinal birth cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium. We examined (a) developmental trajectories of “chronic‐low” versus “typical” prosocial behavior across childhood in a case–control design (N = 2,095), and (b) continuous “low prosocial” scores at comparable cross‐cohort time‐points (N = 2,121). Meta‐analyses were performed to examine differentially methylated positions and regions. At the cohort‐specific level, three CpGs were found to associate with chronic low prosocial behavior; however, none of these associations was replicated in another cohort. Meta‐analysis revealed no epigenome‐wide significant CpGs or regions. Overall, we found no evidence for associations between DNAm patterns at birth and low prosocial behavior across childhood. Findings highlight the importance of employing multi‐cohort approaches to replicate epigenetic associations and reduce the risk of false positive discoveries.

Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders

“…Studies investigating whether these differences in DNAm remain, amplify, or attenuate with age are advised, as well as how sensitive these signatures are in the context of intervention (anti-inflammatory medications and treatments, as well as lifestyle interventions such as the cessation of smoking in pregnancy). There is also precedent to examine whether composite methylation proxies of inflammation differ across psychopathology (144) or specific neurological cases such as Cerebral Palsy or neurodevelopmental disorders such as Fragile X syndrome, autism and ADHD, given examples of other poly-epigenetic signatures of psychiatric disorders (145). Future work that focuses on such DNAm dynamics in relation to these outcomes in ongoing longitudinal studies of infants born preterm is therefore of interest, as well as replication in different population samples.…”

“…There is also precedent to examine whether composite methylation proxies of inflammation differ across psychopathology (144) or specific neurological cases such as Cerebral Palsy or neurodevelopmental disorders such as Fragile X syndrome, autism and ADHD, given examples of other poly-epigenetic signatures of psychiatric disorders (145). Future work that focuses on such DNAm dynamics in relation to these outcomes in ongoing longitudinal studies of infants born preterm is therefore of interest, as well as replication in different population samples.…”

Epigenome-wide association study of long-term psychosocial stress in older adults

“…At each CpG site, DNA methylation was quantified using beta values, which approximate the proportion of methylation, making them biologically interpretable. To ensure that strong outliers were not driving the results, we winsorized methylation values that were greater than three times the interquartile range (IQR) of the 25 th and the 75th percentiles [ 36 , 37 ]. The Houseman Method was used to estimate white blood cell proportions [ 38 ].…”