Genetics of migraine: complexity, implications, and potential clinical applications

Migraine is a common neurological disorder with large burden in terms of disability for individuals and costs for society. Accurate diagnosis and effective treatments remain priorities. Understanding the genetic factors that contribute to migraine risk and symptom manifestation could improve individual management. Migraine has a strong genetic basis that includes both monogenic and polygenic forms. Some distinct, rare, familial migraine subtypes are caused by pathogenic variants in genes involved in ion transport and neurotransmitter release, suggesting an underlying vulnerability of the excitatory-inhibitory balance in the brain, which might be exacerbated by disruption of homoeostasis and lead to migraine. For more prevalent migraine subtypes, genetic studies have identified many susceptibility loci, implicating genes involved in both neuronal and vascular pathways. Genetic factors can also reveal the nature of relationships between migraine and its associated biomarkers and comorbidities and could potentially be used to identify new therapeutic targets and predict treatment response.