Fig. 3
Methylation and genotype correlations by distance. We took the top three meQTL effects by p value in the study overall and plotted the distribution of methylation–methylation (Meth–Meth) correlation, meQTL effects (SNP–Meth) and SNP–SNP correlation around these findings. The top panels show several megabases around the top methylation site overall, chr22:39,040,217–39,040,773 (p = 8.08 × 10−177); the middle panels show the region around site chr14:32,953,580–32,954,000 (p = 1.10 × 10−167), while the bottom panels show the region around site chr3:192,884,173–192,884,636 (p = 5.71 × 10−165). Correlated blocks of SNPs in close proximity show association with the same methylation site(s). This leads to the horizontal “stripes” of significant meQTL associations. However, SNPs also tend to be associated with methylation levels at several sites on the same haplotype, leading to the two-dimensional patchwork of “striped squares” along the diagonal (see detail in SNP-Meth panels). This trend was observed universally in the genome, from small LD blocks measuring a few kilobases to very large regions, such as exists around the MHC on chromosome 6 (Supplementary Material in Additional file 1, p. 11). This serves to illustrate that while SNPs and their associated methylation sites tend to be co-localized, significant LD extending for many megabases can generate apparently long-range effects