Fig. 6
From: DNA methylation as a mediator of HLA-DRB1*15:01 and a protective variant in multiple sclerosis
Association of methylation-mediated SNPs with multiple sclerosis (MS). a Association between SNPs and MS in the Scandinavian cohort (SCAND, 8172 cases and 13,263 controls) after adjustment for four PCAs (upper panel), the DRB1*15:01 associated terms (middle panel) and all 13 established MS risk variants in the HLA locus5 (lower panel) (for details see Methods). b Association between SNPs and MS based on meta-analysis of SCAND and three additional cohorts from Sweden (SWE), Germany (DE), and Iceland (ICE) (upper panel, 14,259 cases and 171,347 controls) and Forest plots (lower panel) representing odds ratios (OR, square, proportional to weight) and associated confidence intervals for each cohort and the summary measure (diamond) for the significant (rs9267649) and suggestive (rs2227956) SNPs, with dotted vertical line of no effect. a, b The –log10(p-value) of 47 out of 50 SNPs and their position on chromosome 6 are given on the y- and x-axis, respectively. Colors of circles correspond to different thresholds of statistical significance, red: p-value < 5 × 10−8 (genome-wide significance), orange: 1 × 10−5 < p-value < 5 × 10−8 (suggestive significance) and black: p-value ≥ 1 × 10−5 (non-significant). c Methylation values at DMR3 (exon 2) of HLA-DRB1 gene in DRB1*15:01 heterozygous MS patients and healthy controls (n = 183) stratified according to the rs9267649 (left panel) and rs2227956 (right panel) genotype. d HLA-DRB1 gene expression in DRB1*15:01 heterozygous MS patients and non-MS controls (n = 55) stratified for the rs9267649 (left panel) and rs2227956 (right panel) genotype. c, d Significance was estimated using linear regression (for details see Methods)
