Genetic Aspects of Primary Headache

Dear Colleagues,

Primary headache disorders are one of the leading causes of disability worldwide, with a global prevalence among adults of around 50%. These disorders are characterized by recurrent headaches, and associated with personal and societal burdens of pain, disability, damaged quality of life, and financial cost. Nevertheless, headache disorders have been underestimated, under-recognized, and under-treated throughout the world. The primary headaches include four main groups: migraine, tension-type headache, trigeminal autonomic cephalalgias (TACs), and other primary headache disorders. Migraine is the most common primary headache disorder, affecting one in seven people, and has been reported to have a strong genetic component. Rare monogenic subtypes of migraine have been identified, where mutations are found in ion channels, while genetic studies in the common forms of migraine had more limited success until 2010, when the first genome-wide association study (GWAS) was reported for migraine by et al. (Nature Genetics). Since then, more than 40 susceptibility loci that affect risk for migraine have been identified including evidence for involvement of both neuronal and vascular mechanisms. Tension-type headache has so far been reported to be caused by a combination of genetic and environmental factors when frequent, while primarily caused by environmental factors when infrequent. A genetic component has been suggested for the most common form of TACs (cluster headache) involving key regulators of circadian rhythm and the neuropeptide calcitonin gene-related peptide (CGRP), however demonstrated associations presently lack replicability. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare type of TAC. The occurrence of SUNCT has been described, which raises the possibility that SUNCT and possibly other TACs will eventually all be considered to be of genetic predisposition.

This Special Issue of Brain Sciences will focus on the progress that has been made towards understanding the disease mechanisms behind primary headache disorders, with a focus on genetics.

Dr. Andrea Carmine Belin

Dr. Caroline Ran
Guest Editors

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• Migraine
• Cluster headache
• GWAS
• Pain
• Treatment
• CGRP
• Biomarker