For example, a CpG located at chr6:31275580 (upstream of HLA-C region) is one of the top hypomethylated CpGs showing a directionally consistent decrease in DNA methylation levels (> 10%) when comparing ACPA-negative individuals, medium-positive individuals, high-positive individuals, and then RA patients (Fig. 2c). The gene discussed is PRTN3; the disease is rheumatoid arthritis.