Abstract
Cytosine-5 methylation within CpG dinucleotides is a potentially important mechanism of epigenetic influence on human traits and disease. In addition to influences of age and gender, genetic control of DNA methylation levels has recently been described. We used whole blood genomic DNA in a twin set (23 MZ twin-pairs and 23 DZ twin-pairs, N = 92) as well as healthy controls (N = 96) to investigate heritability and relationship with age and gender of selected DNA methylation profiles using readily commercially available GoldenGate bead array technology. Despite the inability to detect meaningful methylation differences in the majority of CpG loci due to tissue type and locus selection issues, we found replicable significant associations of DNA methylation with age and gender. We identified associations of genetically heritable single nucleotide polymorphisms with large differences in DNA methylation levels near the polymorphism (cis effects) as well as associations with much smaller differences in DNA methylation levels elsewhere in the human genome (trans effects). Our results demonstrate the feasibility of array-based approaches in studies of DNA methylation and highlight the vast differences between individual loci. The identification of CpG loci of which DNA methylation levels are under genetic control or are related to age or gender will facilitate further studies into the role of DNA methylation and disease.
Highlights
Epigenetic factors have recently been found to play an important role in developmental plasticity [1,2,3]
Age-related DNA methylation We investigated the association between DNA methylation levels of the 280 high-quality probes with age
Using genomic DNA extracted from peripheral blood, we analyzed DNA methylation patterns of a large number of CpG sites from more than 800 genes spread throughout the genome in 23 monozygotic and 23 dyzygotic healthy twin-pairs and 96 healthy singletons
Summary
Epigenetic factors have recently been found to play an important role in developmental plasticity [1,2,3]. Methylation of CpG-rich promoter areas (CpG islands) has been identified as an important mechanism in the dynamic regulation of gene transcription of mammalian genes [5,6]. DNA methylation is established early in embryogenesis [7] and is the prime mechanism of X-chromosomal inactivation as well as of imprinting effects [8]. Differential DNA methylation can be age-related [9,10], and is involved in a number of disorders including human cancers [11]. As DNA methylation plays an important role in the mechanism of epigenetic memory [12] it is of primary interest for the study of epigenetic influences on human traits and diseases
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