Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans

Abstract

Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypo-methylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period.

Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

“…This does not rule out the possibility that a minority of genes are influenced by a common environment. Indeed, previous genome-scale studies of DNA methylation have found a range of probes significantly associated with maternal environmental, from 0.6% (Breton et al 2009) and 1.1% (Fryer et al 2011) to 23% (Katari et al 2009). Because the accuracy of the estimation of effect size depends on study power, further investigation in larger numbers of twins is needed (Visscher 2004).…”

Make way for the ‘next generation’: application and prospects for genome-wide, epigenome-specific technologies in endocrine research

“…The relative ease of use and ability to analyse multiple samples in parallel has resulted in a recent increase in reports using these arrays on a variety of research areas (e.g. Banister et al 2011, Cotton et al 2011, Fackler et al 2011, Fryer et al 2011, Martino et al 2011. Although these arrays, post-sodium bisulphite conversion, report on methylation, it is important to bear in mind that they examine a discrete number of CpGs within a region and not methylation of multiple, contiguous CpGs within, for example, a CpG island.…”

Effects of early-life environment and epigenetics on cardiovascular disease risk in children: highlighting the role of twin studies

“…However, no attempts were made to correlate methylation with gene expression. Other gestational CVD risk factors shown to influence DNA methylation in humans include maternal smoking (60), folate intake (61), and levels of homocysteine (62), which is involved in the development of atherosclerosis by inducing changes in DNA methylation in multiple genes in vascular smooth muscle cells and is the biomarker most directly implicated in epigenetic mechanisms relating to CVD risk (2). Epigenetic marks at these genes are sensitive to the prenatal environment (63).…”