The findings extend reports linking PARP9/miR-505/MRPS18B/RPTOR/FOXO3 hypomethylation and RASGRP4/WIPI2/GNG12 hypermethylation with the clinical phenotypes, or survival in active TB patients, and provide direct evidence that perturbation of PARP9/RASGRP4/WIPI2/FOXO3 signaling through epigenetic programming may play an important role in the mediation of human immune responses against Mtb. In conclusions, we present whole genome DNA methylation analysis in patients with active pulmonary TB and validated several differentially DNA methylation loci by pyro-sequencing in an independent cohort. Here, FOXO3 is linked to tuberculosis.