DNA methylation in complex diseases

In this thesis, we studied genome-wide DNA methylation (methylation array experiments) in the context of complex diseases. We aimed to better understand the association between environment, genetics, and DNA methylation. We performed genome-wide methylation analysis in patients with posttraumatic stress disorder (PTSD), fetal alcohol syndrome (FASD), Beckwith–Wiedemann syndrome (BWS), and the SETD1B-related disorder.
In the PTSD study, we found that genetic factors, epigenetic factors and gender differences were involved in the etiology of PTSD.
In the research on FASD, we focused primarily on epigenetic differences in the individual sub-phenotypes, growth retardation, central nervous system (CNS) damage, and facial abnormalities. In addition, we identified FASD DNA methylation markers, which could facilitate the diagnosis in the future.
Genome-wide methylation analysis carried out in the BWS cohort detected new epigenetic loci related to BWS.
Finally, DNA methylation patterns (episignatures) characteristic for patients with genetic aberrations involving the SETD1B gene were identified aiding diagnostics of this disorder.
The general conclusion from our research is that global DNA methylation analysis can provide important information on the mechanisms responsible for the development of complex diseases. Moreover, these DNA methylation analyses pave the way for designing new diagnostic tests.