Exploring genes and pathways involved in migraine

Abstract

The research in this thesis was aimed at identifying genes and molecular pathways involved in migraine. To this end, two gene expression analyses were performed in brain tissue obtained from transgenic mouse models for familial hemiplegic migraine (FHM), a monogenic subtype of migraine with aura. Next, a study was conducted aimed at analyzing epigenetic marks at migraine candidate genes in FHM mice. In addition to the studies in migraine-relevant mouse models, the genetic architecture of migraine was explored by performing various gene-based pathway analyses to mine the extensive data sets resulting from genome wide association studies (GWAS) for the common forms of migraine. With these data, the overlap in genetic architecture of migraine with aura (MA) and migraine without aura (MO) was explored, as well as the cell types and

brain regions that are likely involved in the pathophysiology of migraine and the two migraine subtypes. Finally, a gene expression profiling study was performed in blood of patients suffering

from primary headache, in this case cluster headache. Combining the various approaches let to the identification of migraine-relevant genes, pathways and cell types that helps to unravel pathophysiological mechanisms of migraine and other primary headache disorders.