Fig. 5

Interactions between DNA methylation and local sequence context at some top ESS regions. a–d Average methylation vs. SNP genotype at ESS regions within CYP2E1, DUSP22, SPATC1L, and ZFP57. In each panel, gene diagram (top) shows location of ESS region where methylation analysis was performed (asterisk) relative to that of a SNP that was genotyped in 64 Gambian children. Grid summarizes normalized linkage disequilibrium (D’) across these ~3-kb regions in a Gambian population in Western Gambia (GWD, 1000 Genomes Project [80]). With the exception of G/G individuals at rs3129057 (ZFP57), there is substantial interindividual variation in average methylation within each genotype class. At CYP2E1 (a), average methylation is not associated with SNP genotype (P = 0.31). At DUSP22, SPATC1L, and ZFP57 (b–d) average methylation is associated with genotype (P = 0.002, 0.02, and 0.0001, respectively). At these same loci, interindividual variance differs between the two homozygous genotypes; i.e., C/C vs. T/T at DUSP22 (P = 0.02), G/G vs. A/A at SPATC1L (P = 0.04), and G/G vs. A/A at ZFP57 (P = 1.9 × 10^–6). e, f Clonal bisulfite sequencing data at two homozygous individuals at each of SPATC1L and ZFP57, respectively, confirm dramatic interindividual variation in DNA methylation in the absence of local sequence variation. Black, empty, and gray circles represent methylated, unmethylated, and indeterminate CpG sites, respectively. Vertical red line indicates the position of the SNP