Aims: Migraine is the most common cause of chronic episodic severe headache, and affects 15% of the adult population with considerable burden to individuals and society. Although heritability is estimated to 50-60%, it was not until 2010 that the first genetic variant associated to the common forms of migraine was reported from a genome-wide association study (GWAS) of migraine with aura (Anttila et al, Nat. Genet., 2010). Since then one more GWAS of migraine has been published (Chasman et al, Nat. Genet., 2011), identifying three additional loci. Through this collaborative effort to perform a large-scale meta-analysis of GWAS data for migraine, our main aim is to detect (identify) the genetic mechanisms that underlie migraine. Specific aims include identifying common genetic variants that predispose to the development of migraine and its subtypes (migraine with aura, migraine without aura), as well as several follow-up analyses (see the attached analysis plan).

Hypotheses: We hypothesize that both common and low-frequency variants in the human genome contribute to the susceptibility for migraine, and that a high resolution meta-analysis of GWAS data can identify regions which contain sequence variants predisposing to the trait.

Exposure variables: Genetic variants as identified by GWAS genotyping.

Outcome variables: Presence of self-reported migraine (as identified by answers to questionnaire).