Abstracts

Rationale: The comorbidity of migraine and epilepsy is well established but the genetics of this comorbidity remains unclear. Here we investigate the shared genetic effects on migraine and epilepsy in the Epilepsy Phenome/Genome Project (EPGP) cohort by examining the relationship of migraine prevalence to family history of epilepsy. Methods: EPGP is an ongoing multi-site epilepsy genetics consortium whose goal is to recruit, perform detailed phenotyping on, and collect DNA from 3,750 participants with epilepsy and 1,500 parent controls. The analysis presented here is restricted to a subset of the cohort consisting of sibling and parent-child pairs with non-acquired focal epilepsy (NAFE) and idiopathic generalized epilepsy (IGE). Information on headache was collected in EPGP using a validated instrument. We restricted our analyses to individuals over 12 years of age because the instrument is validated for respondents ≥12 years. We analyzed the predictors of migraine in current EPGP data. According to the current International Headache Society diagnostic criteria, migraine with aura (MA) and migraine without aura (MO) are not mutually exclusive; hence to distinguish the predictors of MA and MO, we defined a new category consisting of MO without MA (MO "only"). In the EPGP screening interviews, participants were asked to report additional relatives (beyond the affected sibling or parent-child pair) affected with epilepsy or a seizure disorder. We identified 1,155 additional relatives reported to have seizure disorders who were not enrolled in EPGP; 380 of these were first degree relatives of enrolled participants. We examined migraine prevalence and subtypes in enrolled participants in relation to family history of seizure disorders in these additional relatives for 917 enrolled EPGP participants with IGE or NAFE in 570 EPGP families. Results: Prevalence of a history of migraine in EPGP was much higher than that in population-based series: for females 33% vs. 18%, for males 16% vs. 6%, respectively. Prevalence did not differ by epilepsy type. Prevalence of migraine in EPGP enrolled participants increased with increasing number of additional relatives reported to have seizure disorders in the family. This increase was most pronounced for the number of affected first-degree relatives with epilepsy, and most pronounced when ≥2 additional relatives (beyond the enrolled pair) were reported to have seizure disorders. The increase in prevalence of migraine with increasing number of additional reported affected relatives with epilepsy was seen in both MA and MO but was more prominent for MA than MO (Figure 1). The relationship between number of additional individuals with seizure disorders and migraine prevalence in the enrolled relatives persisted in both IGE and NAFE. Conclusions: These findings support a shared genetic susceptibility for epilepsy and migraine that is stronger for MA, and present in both IGE and NAFE.