Differential methylation in the discovery cohort of ClinR
Whole blood DNA methylation levels at seven individual CpG sites and 60 differentially methylated regions (DMR) were significantly associated with ClinR (Figure 2a, Table 2, Table S1). The Q-Q plot (Figure S2a) and the inflation factor λ of 1.064 indicated no obvious inflation of the results. Three out of the seven CpG sites were significantly correlated with gene-expression level in cis (FDR<0.05), resulting in four CpG-gene pairs that showed negative correlation (Table S2). These four eQTM genes were enriched in two pathways: G Protein Signaling Pathways and Hemostasis (P<0.01, Table S3)
We also identified four epigenome-wide significant CpG sites and 67 DMRs that associated with ClinR in nasal brushes (Table S4-S5). The Q-Q plot (Figure S3a) and the λ of 1.125 indicated no obvious inflation of the results. We verified the CpG sites identified from whole blood samples in nasal brushes, and found that one CpG (cg15404785) associated with ClinR showed nominal significance (P<0.05) and the same direction of effect in nasal brushes (Table S6). Four ClinR-associated CpG sites were correlated to expression level of four genes incis (nominal significant P<0.05) in nasal brushes, with one pair (cg07673230-RPL30 (Ribosomal Protein L30)) also being nominal significant and in the same direction in the PIAMA dataset (Table S7).