Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained~25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.

Background Early life environments induce long-term changes in neurocognitive development and behaviour. In animal models, early environmental cues affect neuropsychological phenotypes via epigenetic processes but, as yet, there is little direct evidence for such mechanisms in humans.Method We examined the relation between DNA methylation at birth and child neuropsychological outcomes in two culturally diverse populations using a genome-wide methylation analysis and validation by pyrosequencing.Results Within the UK Southampton Women’s Survey (SWS) we first identified 41 differentially methylated regions of interest (DMROI) at birth associated with child’s full-scale IQ at age 4 years. Associations between HES1 DMROI methylation and later cognitive function were confirmed by pyrosequencing in 175 SWS children. Consistent with these findings, higher HES1 methylation was associated with higher executive memory function in a second independent group of 200 SWS 7-year-olds. Finally, we examined a pathway for this relationship within a Singaporean cohort (n = 108). Here, HES1 DMROI methylation predicted differences in early infant behaviour, known to be associated with academic success. In vitro, methylation of HES1 inhibited ETS transcription factor binding, suggesting a functional role of this site.Conclusions Thus, our findings suggest that perinatal epigenetic processes mark later neurocognitive function and behaviour, providing support for a role of epigenetic processes in mediating the long-term consequences of early life environment on cognitive development.

Small‐scale eye‐tracking research lends support to behavioral studies of relational memory by 6 months of life. Here, in the largest eye‐tracking test of relational memory to date (n = 276), we replicate these findings and examine the impact of excluding data based on looking behavior characteristics at test. Past work examining infants' preferential looking toward arbitrary‐paired objects and scenes has excluded infants from analysis based upon “insufficient looking” at test. Yet, research suggests that variation in looking behavior may be associated with looking patterns during encoding, as well as trait‐like differences in visual and cognitive processing. Similar to past research, we observed evidence for relational memory among 6‐month‐olds. In keeping with past research, when infants were excluded based on “insufficient looking,” we observed evidence for relational memory only when infants were tested immediately. However, when exclusion criteria were relaxed, infants specifically demonstrated preferential looking during a presumably more difficult delay‐plus‐interference condition. Moreover, analyses revealed that looking behavior during encoding was associated with looking behavior at test. Together, results suggest that infants do possess rudimentary relational memory capabilities, but that experimenters' ability to detect these capabilities is influenced by both experimental conditions and individual differences in looking behavior.

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