Abstract
BackgroundChanges in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements.ResultsUsing a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels.ConclusionsThese results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.
Highlights
Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, cancer
The distribution of maternal ages was skewed towards younger mothers, with 41% (N = 69) being younger than 26 and the proportion diminishing with increasing age (Table 1; 26-30 yrs, 33%, N = 55; 31-35 yrs, 20%, N = 34; 36-39 yrs, 6%, N = 10)
Most mothers were classified as normal weight or overweight at the time of recruitment according to body mass index (BMI), with 5.4% (N = 9) mothers being underweight (BMI < 18.5), 46% (N = 77) normal (BMI = 18.5 - 24.9), 20% (N = 34) overweight (BMI = 25 - 29.9), and 29% (N = 48) obese (BMI > 29.9)
Summary
Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, cancer. Replication results were not presented for all significant CpGs, but focusing on only those mapped to polycomb group proteins the 64 genes with hypermethylated sites replicated in other tissues and individuals, while the 11 hypomethylated genes generally did not. Once again, this could be due to changes in blood cell composition with age
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