Thesis defense Mandy Meijer (Donders series 591)

7 March 2023

Promotors: prof. dr. B. Franke, prof. C. Sandi, prof. M. Klein

Epigenetics in externalizing behaviours: linking the environment and genome through epigenetics as a key to understanding externalizing behaviours

Externalizing behaviours are any behaviour that manifests in one’s outward behaviour and reflects a person’s negative interaction with their surroundings. The exact aetiology of externalizing behaviours remains unclear, but both genetic and environmental factors contribute to these behaviours. I aimed to increase our understanding of the biological mechanisms underlying different externalizing disorders and traits through identification of epigenetic patterns (DNA methylation and histone tail modifications) as a link between genetic and environmental factors underlying externalizing behaviours. For this purpose, we performed epigenetic association studies with several different experimental approaches. I identified cholesterol metabolism and immune functioning as putative molecular mechanisms involved in externalizing behaviours. However, before drawing robust conclusions, the results obtained by our association studies should be replicated and verified in experimental studies, e.g., making use of animal models. The work I described in this thesis taught us lessons about the required study set-ups to successfully perform epigenetic studies in externalizing behaviours. Most importantly, future studies should focus on reducing heterogeneity, increasing sample sizes, integration of multiple -omics datasets, and performing cross-species experiments and analyses.