Allele-specific methylation of imprinted genes in fetal cord blood is influenced by cis-acting genetic variants and parental factors

Aim: To examine the effects of genetic variation, parental age and BMI on parental allele-specific methylation of imprinted genes in fetal cord blood samples. Methodology: We have developed SNP genotyping and deep bisulphite sequencing assays for six imprinted genes to determine parental allele-specific methylation patterns in diploid somatic tissues. Results: Multivariate linear regression analyses revealed a negative correlation of paternal age with paternal MEG3 allele methylation in fetal cord blood. Methylation of the maternal PEG3 allele showed a positive correlation with maternal age. Paternal BMI was positively correlated with paternal MESTallele methylation. In addition to parental origin, allele-specific methylation of most imprinted genes was largely dependent on the underlying SNP haplotype. Conclusion: Our study supports the idea that parental factors can have an impact, although of small effect size, on the epigenome of the next generation, providing an additional layer of complexity to phenotypic diversity.