Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jun 1;7(6):594-605.
doi: 10.4161/epi.20117. Epub 2012 Jun 1.

Individual Variation and Longitudinal Pattern of Genome-Wide DNA Methylation From Birth to the First Two Years of Life

Affiliations
Free PMC article

Individual Variation and Longitudinal Pattern of Genome-Wide DNA Methylation From Birth to the First Two Years of Life

Deli Wang et al. Epigenetics. .
Free PMC article

Abstract

Prenatal development and early childhood are critical periods for establishing the tissue-specific epigenome, and may have a profound impact on health and disease in later life. However, epigenomic profiles at birth and in early childhood remain largely unexplored. The focus of this report is to examine the individual variation and longitudinal pattern of genome-wide DNA methylation levels from birth through the first two years of life in 105 Black children (59 males and 46 females) enrolled at the Boston Medical Center. We performed epigenomic mapping of cord blood at birth and venous blood samples from the same set of children within the first two years of life using Illumina Infinium Humanmethylation27 BeadChip. We observed a wide range of inter-individual variations in genome-wide methylation at each time point including lower levels at CpG islands, TSS200, 5'UTR and 1st Exon locations, but significantly higher levels in CpG shores, shelves, TSS1500, gene body and 3'UTR. We identified CpG sites with significant intra-individual longitudinal changes in the first two years of life throughout the genome. Specifically, we identified 159 CpG sites in males and 149 CpG sites in females with significant longitudinal changes defined by both statistical significance and magnitude of changes. These significant CpG sites appeared to be located within genes with important biological functions including immunity and inflammation. Further studies are needed to replicate our findings, including analysis by specific cell types, and link those individual variations and longitudinal changes with specific health outcomes in early childhood and later life.

Figures

None
Figure 1. Gender specific distributions [(A) male, (B) female] of methylation levels of 27K CpG sites at two time points. CB stands for cord blood and PB stands for postnatal blood. The y-axis is the proportions of CpG sites corresponding to methylation categories specified by the x-axis. A bimodal distribution pattern was observed for both cord and postnatal blood samples. Comparisons of proportions of CpG sites in different methylation categories were conducted between males and females, and between cord and postnatal blood samples using Wilcoxon Rank Sum test or Wilcoxon Signed-Rank test. The FDR adjusted p-values are presented in the table below the figure.
None
Figure 2. Six major types of DNA methylation distributions across 105 samples. The number of CpG sites (and the proportion) with each specific distribution is presented in the table below the figure. Bimodal (A) and unimodal distributions (B to F) were identified using the DIP test (the threshold value for combined samples is 0.051, for male samples is 0.074, and for female samples is 0.067). Kurtosis (K) and Skewness (S) parameters were used to further classify unimodal distributions into five categories: (B) S < -0.03, (C) S > 0.03, (D) -0.03 ≤ S ≤ 0.03 and K > 0.05, (E) -0.03 ≤ S ≤ 0.03 and -0.05 ≤ K ≤ 0.05, and (F): -0.03 ≤ S ≤ 0.03 and K < -0.05. The kurtosis was estimated using the moment method and then subtract 3.
None
Figure 3. Distributions of mean methylation levels are presented at different CpG island groups for cord blood samples at birth (A) and postnatal venous samples within 2 y of life (B). For each boxplot, the dot in the box represents the mean methylation level, and the horizontal bar in the box is the median methylation level. The two horizontal bars below the 25th percentile bars (the bottom side of the box) reflect the minimum and 5th percentile, respectively. Similarly, the top two bars above the 75th percentile (the top side of the box) reflect the 95th percentile and the maximum, respectively. The lower two panels are density plots of changes in methylation levels (postnatal minus cord) for males (C) and females (D), respectively.
None
Figure 4. Distributions of mean methylation levels are presented at different locations of the gene structures at two time points. For each boxplot, the dot in the box represents the mean methylation level, and the horizontal bar in the box is the median methylation level. Two horizontal bars below the 25th percentile bar (the bottom side of the box) reflect the minimum and 5th percentile, respectively. Similarly, the top two bars above the 75th percentile bar (the top side of the box) reflect the 95th percentile and the maximum, respectively. The lower two panels are probability density plots of the mean methylation level changes (postnatal minus cord) for males and females, respectively.

Similar articles

  • DNA methylation in childhood asthma: an epigenome-wide meta-analysis.
    Xu CJ, Söderhäll C, Bustamante M, Baïz N, Gruzieva O, Gehring U, Mason D, Chatzi L, Basterrechea M, Llop S, Torrent M, Forastiere F, Fantini MP, Carlsen KCL, Haahtela T, Morin A, Kerkhof M, Merid SK, van Rijkom B, Jankipersadsing SA, Bonder MJ, Ballereau S, Vermeulen CJ, Aguirre-Gamboa R, de Jongste JC, Smit HA, Kumar A, Pershagen G, Guerra S, Garcia-Aymerich J, Greco D, Reinius L, McEachan RRC, Azad R, Hovland V, Mowinckel P, Alenius H, Fyhrquist N, Lemonnier N, Pellet J, Auffray C; BIOS Consortium, van der Vlies P, van Diemen CC, Li Y, Wijmenga C, Netea MG, Moffatt MF, Cookson WOCM, Anto JM, Bousquet J, Laatikainen T, Laprise C, Carlsen KH, Gori D, Porta D, Iñiguez C, Bilbao JR, Kogevinas M, Wright J, Brunekreef B, Kere J, Nawijn MC, Annesi-Maesano I, Sunyer J, Melén E, Koppelman GH. Xu CJ, et al. Lancet Respir Med. 2018 May;6(5):379-388. doi: 10.1016/S2213-2600(18)30052-3. Epub 2018 Feb 26. Lancet Respir Med. 2018. PMID: 29496485
  • Evidence for age-related and individual-specific changes in DNA methylation profile of mononuclear cells during early immune development in humans.
    Martino DJ, Tulic MK, Gordon L, Hodder M, Richman TR, Metcalfe J, Prescott SL, Saffery R. Martino DJ, et al. Epigenetics. 2011 Sep 1;6(9):1085-94. doi: 10.4161/epi.6.9.16401. Epub 2011 Sep 1. Epigenetics. 2011. PMID: 21814035
  • Longitudinal study of DNA methylation during the first 5 years of life.
    Urdinguio RG, Torró MI, Bayón GF, Álvarez-Pitti J, Fernández AF, Redon P, Fraga MF, Lurbe E. Urdinguio RG, et al. J Transl Med. 2016 Jun 3;14(1):160. doi: 10.1186/s12967-016-0913-x. J Transl Med. 2016. PMID: 27259700 Free PMC article.
  • Focussing reduced representation CpG sequencing through judicious restriction enzyme choice.
    Kirschner SA, Hunewald O, Mériaux SB, Brunnhoefer R, Muller CP, Turner JD. Kirschner SA, et al. Genomics. 2016 Apr;107(4):109-19. doi: 10.1016/j.ygeno.2016.03.001. Epub 2016 Mar 3. Genomics. 2016. PMID: 26945642
  • Emerging patterns of epigenomic variation.
    Milosavljevic A. Milosavljevic A. Trends Genet. 2011 Jun;27(6):242-50. doi: 10.1016/j.tig.2011.03.001. Epub 2011 Apr 18. Trends Genet. 2011. PMID: 21507501 Free PMC article. Review.
See all similar articles

Cited by 34 articles

See all "Cited by" articles

Publication types

Substances

LinkOut - more resources

Feedback