Fig. 2
Some HM450 probes exhibit epigenetic supersimilarity (ESS). a Distribution of probe-specific narrow-sense heritability (h2) estimates from [9]. (Shown are data on 24,839 probes; 9566 probes with h2 < 0.001 were excluded for clarity.) Of the probes, 1058 show h2 > 1, including most of the probes illustrated in Fig. 1 (red box plot). b Normalized DZ MSE vs. MZ MSE for the 34,405 probes (top 10%) from Grundberg et al. [9]. Histograms (right and top) show distribution; red curves show best normal fit. Normalized DZ MSE (mean ± standard deviation = 0.76 ± 0.13) is normally distributed, but normalized MZ MSE (0.63 ± 0.23) is skewed left (P = 7.0 × 10–66). Probes with h2 > 1 are shown in blue. Probes to the left of the green line (y = 2x) are classified as ESS. c Associations between probe-level mQTL and heritability estimates (both from Grundberg et al. [9]). Among the 9708 probes that are both in the top 10% of interindividual variance and positive for mQTL (top panel) mean heritability is 0.64 (gray vertical line) and positively associated with the strength of mQTL. Among ESS probes positive for mQTL (middle panel), mean heritability is 0.90 and not associated with mQTL. Mean heritability of ESS probes negative for mQTL (0.99, bottom panel) is similar to that of mQTL-positive ESS probes. d Model to explain ESS in MZ twins. Numbers on the dice represent different methylation states at a specific locus. If de novo methylation occurs after embryo cleavage (top), each MZ embryo undergoes independent establishment. If de novo methylation occurs prior to embryo cleavage (bottom), both MZ embryos inherit the same methylation state. e Consistent with this model, bisulfite pyrosequencing in three tissues of 17 cadavers indicates that ESS probes also show systemic interindividual variation. Two examples are shown, OR2L13 and HLA-DQB2