To illustrate this point, we overlapped the identified target CpGs with existing EWAS results (Additional file 13: Table S13) and found that target CpGs of several genes were enriched for trait-associated CpGs, including Werner syndrome (SENP7, a SUMO peptidase; SUMO modifies the Werner syndrome gene product [39, 40]), auto-immune diseases and inflammatory markers (NLRC5, a key regulator of MHC class I-dependent immune response [35]), and obesity/BMI (NFKBIE and NFKB1; NFκB is a central regulator of inflammatory response, including metabolism-related inflammation [33]). The gene discussed is NLRC5; the disease is obesity due to melanocortin 4 receptor deficiency.