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Review
. 2023 Feb 20;24(1):12.
doi: 10.1186/s10194-023-01547-8.

Genetics of migraine: where are we now?

Lou Grangeon #  1 , Kristin Sophie Lange #  2   3 , Marta Waliszewska-Prosół  4 , Dilara Onan  5 , Karol Marschollek  4 , Wietse Wiels  6 , Petr Mikulenka  7 , Fatemeh Farham  8 , Cédric Gollion  9 , Anne Ducros  10 ; European Headache Federation School of Advanced Studies (EHF-SAS)
Affiliations
Review

Genetics of migraine: where are we now?

Lou Grangeon et al. J Headache Pain. .

Abstract

Migraine is a complex brain disorder explained by the interaction of genetic and environmental factors. In monogenic migraines, including familial hemiplegic migraine and migraine with aura associated with hereditary small-vessel disorders, the identified genes code for proteins expressed in neurons, glial cells, or vessels, all of which increase susceptibility to cortical spreading depression. The study of monogenic migraines has shown that the neurovascular unit plays a prominent role in migraine. Genome-wide association studies have identified numerous susceptibility variants that each result in only a small increase in overall migraine risk. The more than 180 known variants belong to several complex networks of "pro-migraine" molecular abnormalities, which are mainly neuronal or vascular. Genetics has also highlighted the importance of shared genetic factors between migraine and its major co-morbidities, including depression and high blood pressure. Further studies are still needed to map all of the susceptibility loci for migraine and then to understand how these genomic variants lead to migraine cell phenotypes.

Keywords: Familial hemiplegic migraine; Genetics; Genome-wide association studies; Migraine; Polygenic.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of migraine and genetics. An overview of the complex genetic architecture of migraine, from polygenic model on the left, to monogenic model on the right. Created with BioRender.com
Fig. 2
Fig. 2
Genetics of familial hemiplegic migraine (FHM). Glutamatergic synapse of the central nervous system with proteins encoded by genes involved in familial hemiplegic migraine and their functional roles. Created with BioRender.com
Fig. 3
Fig. 3
Shared genetic background of migraine and its comorbid diseases. Genetic relation of migraine and some of its clinically most relevant comorbidities. Dotted arrow: Genetic association or correlation as demonstrated by GWAS or genetic correlation studies. Solid arrow: Causal association of genetic variants as demonstrated by Mendelian randomization studies. +, liability to one disease increases risk for the comorbidity; −, liability to one disease decreases risk for the comorbidity; ADHD, attention deficit hyperactivity disorder; BP, blood pressure; CAD, coronary artery disease; CeAD, cervical artery dissection. Created with BioRender.com
See this image and copyright information in PMC

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