We also note that many of these neuropsychologic and neuropathologic traits are correlated (Table 4) and that many of these traits correlate with advancing age. The age and sex of subjects have very strong effects on the brain’s epigenome and transcriptome; these two variables are important confounders when performing any analyses of ROS and MAP data. Further, one must carefully consider the molecular effects of neuropathologies that confound aging-related analyses as we have shown with the methylome46. Finally, both circadian and seasonal rhythms influence the epigenome and the transcriptome, introducing an important source of variation for many genes that is rarely appreciated47.
