Genome-wide association analysis and gene identification in migraine with aura

Coordinator:    Prof. Dr. med. Christian Kubisch
Institution: Institut für Humangenetik, Universität zu Köln
The common forms of migraine, i. e. migraine with aura (MA) and migraine without aura (MO), are complex inherited periodic disorders of the central nervous system characterized by a disturbance of neuronal excitability. Due to the very high lifetime prevalence of about 15%, migraine represents a major problem for public health and is estimated to be the most costly neurological disorder in Europe. In contrast to monogenic forms of migraine, which - like many forms of epilepsy - are caused by mutations in ion transport proteins, the molecular basis of MA and MO is elusive. The main goal of this subproject therefore is the first identification of susceptibility genes for MA by a whole genome association (WGA) approach in a large and clinically well characterized MA sample. The most significant findings will be replicated in a sample consisting of several thousand MA patients collected in the framework of an international consortium for migraine genetics. Moreover, we will re-investigate our findings in a large MO sample, in which a WGA is performed in parallel in our consortium and the international initiative, allowing for a joined analysis of data and for the thorough understanding which genetic factors are shared between and which are unique for MA and MO. As there are compelling clinical, pharmacological, and genetic data for an overlapping molecular basis of migraine and epilepsy - the other common and periodic neurological hyperexcitability disorder - we will in this consortium also analyze our best WGA results in epilepsy and vice versa. Replicated MA susceptibility genes will be analyzed by in vitro and in vivo models to better understand the pathogenesis of MA and the molecular networks implicated in migraine and the regulation of brain excitability in general. These biochemical, electrophysiological, or molecular follow-up studies will be performed in an integrative and collaborative approach together with other subprojects of our network.
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