Fig. 1

Strategy for identifying correlated regions of systemic interindividual variation (CoRSIVs). a The tissues analyzed represent the three germ layer lineages; 10 Caucasian GTEx donors were studied, yielding 30 methylomes. b Initial unsupervised clustering of whole-genome bisulfite sequencing data; considering all informative bins, they cluster by tissue. c Example of a CoRSIV identified at the PM20D1 promoter. The blue triangle shows a region of correlated methylation comprising thirteen 100-bp bins; the three scatter plots illustrate its high inter-tissue correlation. d Plots of individual methylation at the PM20D1 CoRSIV illustrate systemic interindividual variation. Genotype data at rs708727 (bottom panel) indicate strong mQTL at the locus. e Scatter plot of interindividual methylation range vs. number of CpGs per CoRSIV, for all 39,424 CoRSIVs initially identified. Subsequent analyses focus on the 9926 CoRSIVs with ≥ 5 CpGs/CoRSIV and IIR ≥ 20 (shaded area). f Unlike genome-wide bins, the 9926 CoRSIV bins cluster by individual (B, H, T—brain, heart, thyroid). Box plots on right show that the 10 donors show no individual differences in average methylation across all the CoRSIVs. g An illustrative region from the CoRSIV plot of chr19. Inset shows example of annotation of a CoRSIV (chr19_8726) at ZNF714