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Research Paper

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

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Pages 86-94 | Received 11 Jun 2010, Accepted 21 Aug 2010, Published online: 01 Jan 2011

Figures & data

Figure 1 Density function plots showing the distribution of methylation as reported by infinium array β values. Distribution of β values for the 21,261 CpG sites, separated by (A) those in CpG islands (n = 16,866) and (B) those outside these islands (n = 4,395) for each of the 12 samples.

Figure 1 Density function plots showing the distribution of methylation as reported by infinium array β values. Distribution of β values for the 21,261 CpG sites, separated by (A) those in CpG islands (n = 16,866) and (B) those outside these islands (n = 4,395) for each of the 12 samples.

Figure 2 Hierarchical clustering using BeadArray data across the 12 samples. (A) β values for all 6,532 autosomal CpG sites where values in all samples were ≥0.8 and ≤0.2. (B) Hierarchical clustering results showing two discrete clusters. Sample numbers are shown with birth weight centile in parentheses. (C) Examples of genes showing significant correlations with birth weight centile across the 12 samples.

Figure 2 Hierarchical clustering using BeadArray data across the 12 samples. (A) β values for all 6,532 autosomal CpG sites where values in all samples were ≥0.8 and ≤0.2. (B) Hierarchical clustering results showing two discrete clusters. Sample numbers are shown with birth weight centile in parentheses. (C) Examples of genes showing significant correlations with birth weight centile across the 12 samples.

Figure 3 Venn diagram showing number of autosomal CpG sites significantly associated with each of the three parameters across the 12 samples; birth weight centile, plasma homocysteine concentration and mean LINE-1 methylation.

Figure 3 Venn diagram showing number of autosomal CpG sites significantly associated with each of the three parameters across the 12 samples; birth weight centile, plasma homocysteine concentration and mean LINE-1 methylation.

Figure 4 Examples of two genes BMX (left column) and AMN (right column) with significant correlations with each of (A) mean LINE-1 methylation (%), (B) plasma homocysteine (µmol/L) and (C) birth weight centile (%) (see ). BMX was positively correlated with LINE-1 methylation level (r = 0.631, p = 0.028) and birth weight centile (r = 0.760, p = 0.004) but inversely correlated with plasma homocysteine concentration (r = −0.813, p = 0.002) across the 12 samples. In contrast, AMN inversely correlated with LINE-1 methylation level (r = −0.630, p = 0.028) and birth weight centile (r = −0.637, p = 0.026) but directly correlated with plasma homocysteine concentration (r = 0.709, p = 0.015).

Figure 4 Examples of two genes BMX (left column) and AMN (right column) with significant correlations with each of (A) mean LINE-1 methylation (%), (B) plasma homocysteine (µmol/L) and (C) birth weight centile (%) (see Table 2). BMX was positively correlated with LINE-1 methylation level (r = 0.631, p = 0.028) and birth weight centile (r = 0.760, p = 0.004) but inversely correlated with plasma homocysteine concentration (r = −0.813, p = 0.002) across the 12 samples. In contrast, AMN inversely correlated with LINE-1 methylation level (r = −0.630, p = 0.028) and birth weight centile (r = −0.637, p = 0.026) but directly correlated with plasma homocysteine concentration (r = 0.709, p = 0.015).

Figure 5 Characteristics of the autosomal CpG sites associated with (A) birth weight centile, (B) plasma homocysteine and (C) mean LINE-1 methylation. Pie charts show proportion of associated CpG sites located within (CGI) and outside CpG islands (non-CGI).

Figure 5 Characteristics of the autosomal CpG sites associated with (A) birth weight centile, (B) plasma homocysteine and (C) mean LINE-1 methylation. Pie charts show proportion of associated CpG sites located within (CGI) and outside CpG islands (non-CGI).

Table 1 Characteristics of the hierarchical clustering-generated groups

Table 2 CpG sites demonstrating significant correlations with plasma homocysteine concentration, birth weight centile and mean LINE-1 methylation level

Table 3 Demographic and biochemical characteristics of the sample cohort

Supplemental material

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