Figure 4: DMPs associated with rs7192, rs9275596 and with PA, as well as DMPs that mediate genetic risk in PA.

(a) Diagram showing associations between genotype (rs7192 (blue circle) and rs9275596 (green circle)) and DMPs, and between the genotype-dependent DMPs and PA. The DMPs are denoted by empty circles. Dashed blue (for rs7192) and green (for rs9275596) lines represent significant associations between genotypes and DMPs at P<5 × 10⁻⁸ based on linear regression models (N=218). In between the DMPs and gene tracks are purple bars that represent the genotype-dependent DMPs that are associated with PA based on linear regression models in 73 PA cases and 67 non-PA controls (DMPs as the outcomes). The two DMPs marked with purple triangles are DMP cg15982117 in the HLA-DRB1 gene and DMP cg18024368 in the HLA-DQB1 gene that may mediate genetic risk in PA, as determined by the CIT. (b) DMP cg18024368 in the HLA-DQB1 gene that may mediate the association between the rs7192 genotype and PA risk in 73 PA cases and 67 non-PA controls. The left panel shows the association between the methylation level at DMP cg18024368 and the rs7192 genotype. The middle panel depicts the association between the methylation level at DMP cg18024368 and PA. The blue bars in the left and middle panels represent median methylation levels. The right panel shows the effect size of the observed rs7192–PA associations (represented by ORs based on the logistic regression model) before and after adjusting for the methylation level at DMP cg18024368 (M), as well as adjusting for both the methylation level at DMP cg18024368 (M) and at DMP cg15982117 (M2). Error bars represent the 95% CIs of the estimated ORs.