Figures & data
T1 and Td represent times when DNA sample is collected and disease occurred, respectively (these events are also represented with a square and ‘D’). Tc is the time when a confounding factor (e.g., environmental exposures) affects methylation (denoted with a ‘C’). In the top panel (A–C), DNA sample is collected after disease onset, we observe a positive association between methylation and disease, but cannot distinguish between each of the three scenarios D->M, M-> D and confounding. In the bottom panel (D–F), DNA sample was obtained prior to disease onset, allowing us to rule out D -> M, but both M -> D and confounding are still possibilities.
![Figure 1. Simplified DNA methylation trajectories for a subject without (green solid line) and with disease (dotted blue line) where (A & D) methylation changes as a consequence of disease, or (B & E) disease occurs as a consequence of methylation, or (C & F) there is no causal relationship between disease and methylation (a confounding factor independently affects both disease status and methylation), respectively.T1 and Td represent times when DNA sample is collected and disease occurred, respectively (these events are also represented with a square and ‘D’). Tc is the time when a confounding factor (e.g., environmental exposures) affects methylation (denoted with a ‘C’). In the top panel (A–C), DNA sample is collected after disease onset, we observe a positive association between methylation and disease, but cannot distinguish between each of the three scenarios D->M, M-> D and confounding. In the bottom panel (D–F), DNA sample was obtained prior to disease onset, allowing us to rule out D -> M, but both M -> D and confounding are still possibilities.](/cms/asset/da83033f-1ae5-4bf2-9bbf-025594e9fe40/iepi_a_12325176_f0001.jpg)