Chronic migraine: Genetics or environment?

BACKGROUND: The transition from episodic migraine to chronic migraine, migraine chronification, is usually a gradual process, which involves multiple risk factors. To date, studies of the genetic risk factors for chronic migraine have focused primarily on candidate‐gene approaches using healthy individuals as controls. AIMS AND METHODS: In this study, we used a large cohort of migraine families and unrelated migraine patients (n > 2200) with supporting genotype and whole‐genome sequencing data. We evaluated whether there are any genetic variants, common or rare, with a specific association to chronic migraine compared with episodic migraine. RESULTS: We found no aggregation of chronic migraine in families with a clustering of migraine. No specific rare variants gave rise to migraine chronification, and migraine chronification was not associated with a higher polygenic risk score. Migraine chronification was not associated with allelic associations with an odds ratio above 2.65. Assessment of effect sizes with genome‐wide significance below an odds ratio of 2.65 requires a genome‐wide association study of at least 7500 chronic migraine patients. CONCLUSION: Our results suggest that migraine chronification is caused by environmental factors rather than genetic factors.