Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills

Abstract

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.

DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort

“…A recent meta-analysis examining epigenome-wide associations between DNAm at birth and childhood cognitive skills synthesizing data from eight pregnancy cohorts within the Pregnancy and Childhood Epigenetics (PACE) consortium (N=3300) did not nd substantial evidence that differential cord blood DNAm at individual CpG sites is associated with cognitive skills [19]. We compared our ndings to those from several EWAS investigating DNAm and cognitive development examined in the PACE study, However, no overlap was identi ed between our ndings and those of previous studies [19,54] .…”

“…With the rise of high-throughput genomics, the eld of epigenetics has undergone rapid development. Epigenetic modi cation, speci cally DNA methylation (DNAm), has been linked to a number of neuropsychiatric outcomes such as severe neurodevelopmental delay, schizophrenia, ASD, and ADHD [14][15][16][17][18][19][20]. DNAm is known to play a key role in embryonic development and has been hypothesized to impact neural stem cell differentiation and maintenance [21], thereby affecting neuropsychiatric outcomes throughout the life course.…”

Epigenetics and ADHD: Reflections on Current Knowledge, Research Priorities and Translational Potential

“…This is crucial because use of neonatal DNAm as a predictive tool for early risk detection would require defining the boundaries of what is being predicted. Interestingly, other recent meta-analyses from the PACE consortium (using largely overlapping datasets as those in Neumann et al [ 72 ]) did not mirror the ADHD finding that epigenetic patterns at birth were associated with other mental or physical health outcomes more strongly than epigenetic patterns measured later in childhood (e.g., cognition [ 81 ], general psychopathology [ 82 ], BMI [ 83 ]), supporting a degree of specificity. On the other hand, there is preliminary evidence that, similarly to what was observed for ADHD, peripheral DNAm patterns at birth associate more strongly with trajectories of social communication deficits (one of the hallmarks of ASD) than DNAm patterns at later time points [ 84 ], although findings remain to be confirmed in a multi-cohort setting.…”

DNA Methylation as a Potential Mediator of the Association Between Prenatal Tobacco and Alcohol Exposure and Child Neurodevelopment in a South African Birth Cohort

“…The evidence is weaker for an association between PAE and the cord blood methylome 17 , although there has been some evidence of epigenomic changes in other tissues such as placental or buccal tissue 18 . While there is evidence that PTE and PAE influence DNA methylation in cord blood, not much is known about the subsequent adverse outcomes, such as delayed neurodevelopment 19,20 or about the association between newborn DNAm and child neurodevelopment or related disorders in general [21][22][23] . Thus, the biological mechanisms connecting PTE and PAE, DNAm and child neurodevelopment are largely unknown.…”