Extended Data Fig. 5: Functional genomic context of meQTL SNPs and CpGs.

Panel a: Genomic overlap between chromatin state annotations (15- state model; Roadmap Epigenomics Project and SNPs/CpGs identified by genome-wide association and cross-ancestry replication testing. Results are presented as a heatmap showing the P-values for enrichment (blue) or depletion (yellow) in the respective chromatin state (two-sided t-test). P-values have been Bonferroni-adjusted for the total number of tests (see Methods for details). Panel b: Colocalisation of SNPs and CpG sites in promoter and enhancer chromatin states. The histograms show the frequency at which CpG sites that localise in promoter or enhancer chromatin states have at least one cis-meQTL SNP that localises to the same chromatin state. Observed (turquoise) cis-meQTL pairs colocalise to the same chromatin state more frequently than matched background SNP-CpG pairs (grey). Panel c: Distance distributions for cis SNP-CpG pairs 1) localising to the same state (left), 2) where one entity localises to a promoter/enhancer state and the other to neither promoter nor enhancer state (center) and 3) one entity localises to a promoter and the other to an enhancer state. Panel d: Overlap of SNP-CpG associations with chromatin contacts in primary cells. The x-axis shows the fraction of SNP-CpG pairs that localise within the same topologically associated domain (TAD, left panel) or that overlap with Hi-C contacts (center and right panels). The left panel shows localisation of long-range cis-meQTLs within the same TAD. The center panel shows the overlap of long range cis-meQTLs (same chromosome, distance SNP - CpG > 1Mb) with contacts from promoter capture Hi-C (PCHi-C). The right panel shows overlap of trans-meQTL with Hi-C contacts. The blue vertical arrows indicate the overlap observed in the data. The grey histograms show the distribution of the fraction of randomly sampled SNP-CpG pairs overlapping contact regions for each category.