Identifying common and rare variants in migraine genetic predisposition

Abstract

Migraine is an episodic brain disorder that is characterized by recurrent pain. Etiology of migraine is extremely complex; most likely caused by combination of genetic and environmental risk factors. The aim of the thesis is to examine the role of MTHFR polymorphisms rs1801131 and rs1801133 as risk factors for pediatric migraine; also in migraine subtypes – migraine with aura (MA) and without aura (MO). Second part involved exome sequencing of two family trios to discover novel genetic risk factors for migraine. Candidate gene study of MTHFR did not reveal any statistically significant results. Exome sequencing revealed three novel variants that could precipitate migraine. PDLIM5, PRKCE and SCN9A all affect voltage-gated channels. Mutations in those genes could increase neuronal hyperexcitability and neurotransmitter release, which in turn has been associated with pain and visual aura.