Genetics of Migraine Aura: an Update

Overview

Journal J Headache Pain

Publisher Biomed Central

Date 2020 Jun 7

PMID 32503413

Citations 20

Authors

Irene de Boer

Gisela M Terwindt

Arn M J M van den Maagdenberg

Affiliations

Soon will be listed here.

Abstract

Migraine is a common brain disorder with a large genetic component. Of the two main migraine types, migraine with aura and migraine without aura, the genetic underpinning in the former is least understood. Given the evidence from epidemiological studies in cohorts and families that the genetic contribution is highest in migraine with aura, this seems paradoxical. Various genetic approaches have been applied to identify genetic factors that confer risk for migraine. Initially, so-called candidate gene associations studies (CGAS) have been performed that test DNA variants in genes prioritized based on presumed a priori knowledge of migraine pathophysiology. More recently, genome-wide association studies (GWAS) tested variants in any gene in an hypothesis-free manner. Whereas GWAS in migraine without aura, or the more general diagnosis migraine have already identified dozens of gene variants, the specific hunt for gene variants in migraine with aura has been disappointing. The only GWAS specifically investigating migraine with aura yielded only one single associated single nucleotide polymorphism (SNP), near MTDH and PGCP, with genome-wide significance. However, interrogation of all genotyped SNPs, so beyond this one significant hit, was more successful and led to the notion that migraine with aura and migraine without aura are genetically more alike than different. Until now, most relevant genetic discoveries related to migraine with aura came from investigating monogenetic syndromes with migraine aura as a prominent phenotype (i.e. FHM, CADASIL and FASPS). This review will highlight the genetic findings relevant to migraine with aura.

Citing Articles

An Integrative Migraine Polygenic Risk Score Is Associated with Age at Onset But Not Chronification.

Chase B, Frigerio R, Rubin S, Franada T, Semenov I, Meyers S J Clin Med. 2024; 13(21).

PMID: 39518622 PMC: 11547092. DOI: 10.3390/jcm13216483.

Investigating migraine phenotype and dynamics in women with endometriosis: an observational pilot study.

Merki-Feld G, Dietrich H, Imesch P, Gantenbein A, Sandor P, Schankin C Acta Neurol Belg. 2024; 124(4):1263-1271.

PMID: 38878131 PMC: 11266208. DOI: 10.1007/s13760-024-02484-2.

The Dawn and Advancement of the Knowledge of the Genetics of Migraine.

Zalaquett N, Salameh E, Kim J, Ghanbarian E, Tawk K, Abouzari M J Clin Med. 2024; 13(9).

PMID: 38731230 PMC: 11084801. DOI: 10.3390/jcm13092701.

Unravelling the Genetic Landscape of Hemiplegic Migraine: Exploring Innovative Strategies and Emerging Approaches.

Alfayyadh M, Maksemous N, Sutherland H, Lea R, Griffiths L Genes (Basel). 2024; 15(4).

PMID: 38674378 PMC: 11049430. DOI: 10.3390/genes15040443.

Disappearance of aura symptoms in patients with hemiplegic migraine after patent foramen ovale closure: a case report and literature review.

Wang P, Yao F, Zhang H, Yu Q, Wang Y Front Neurol. 2023; 14:1267100.

PMID: 37900612 PMC: 10602885. DOI: 10.3389/fneur.2023.1267100.

References

Gorji A, Scheller D, Straub H, TEGTMEIER F, Kohling R, Hohling J . Spreading depression in human neocortical slices. Brain Res. 2001; 906(1-2):74-83. DOI: 10.1016/s0006-8993(01)02557-4. View

Gould D, Phalan F, van Mil S, Sundberg J, Vahedi K, Massin P . Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006; 354(14):1489-96. DOI: 10.1056/NEJMoa053727. View

Tam V, Patel N, Turcotte M, Bosse Y, Pare G, Meyre D . Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019; 20(8):467-484. DOI: 10.1038/s41576-019-0127-1. View

. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1):1-211. DOI: 10.1177/0333102417738202. View

Guey S, Mawet J, Herve D, Duering M, Godin O, Jouvent E . Prevalence and characteristics of migraine in CADASIL. Cephalalgia. 2015; 36(11):1038-1047. DOI: 10.1177/0333102415620909. View

Pelzer N, de Vries B, Kamphorst J, Vijfhuizen L, Ferrari M, Haan J . PRRT2 and hemiplegic migraine: a complex association. Neurology. 2014; 83(3):288-90. DOI: 10.1212/WNL.0000000000000590. View

Stam A, Kothari P, Shaikh A, Gschwendter A, Jen J, Hodgkinson S . Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain. 2016; 139(11):2909-2922. PMC: 5091044. DOI: 10.1093/brain/aww217. View

Andres-Enguix I, Shang L, Stansfeld P, Morahan J, Sansom M, Lafreniere R . Functional analysis of missense variants in the TRESK (KCNK18) K channel. Sci Rep. 2012; 2:237. PMC: 3266952. DOI: 10.1038/srep00237. View

Gormley P, Anttila V, Winsvold B, Palta P, Esko T, Pers T . Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat Genet. 2016; 48(8):856-66. PMC: 5331903. DOI: 10.1038/ng.3598. View

10.

Anttila V, Bulik-Sullivan B, Finucane H, Walters R, Bras J, Duncan L . Analysis of shared heritability in common disorders of the brain. Science. 2018; 360(6395). PMC: 6097237. DOI: 10.1126/science.aap8757. View

11.

Gasparini C, Sutherland H, Griffiths L . Studies on the pathophysiology and genetic basis of migraine. Curr Genomics. 2014; 14(5):300-15. PMC: 3763681. DOI: 10.2174/13892029113149990007. View

12.

Capuani C, Melone M, Tottene A, Bragina L, Crivellaro G, Santello M . Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2. EMBO Mol Med. 2016; 8(8):967-86. PMC: 4967947. DOI: 10.15252/emmm.201505944. View

13.

Anttila V, Stefansson H, Kallela M, Todt U, Terwindt G, Calafato M . Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1. Nat Genet. 2010; 42(10):869-73. PMC: 2948563. DOI: 10.1038/ng.652. View

14.

Thomsen L, Olesen J, Russell M . Increased risk of migraine with typical aura in probands with familial hemiplegic migraine and their relatives. Eur J Neurol. 2003; 10(4):421-7. DOI: 10.1046/j.1468-1331.2003.00621.x. View

15.

Hasan M, Fermaintt C, Gao N, Sakai T, Miyazaki T, Jiang S . Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation. Immunity. 2015; 43(3):463-74. PMC: 4575271. DOI: 10.1016/j.immuni.2015.07.022. View

16.

Heron S, Dibbens L . Role of PRRT2 in common paroxysmal neurological disorders: a gene with remarkable pleiotropy. J Med Genet. 2013; 50(3):133-9. DOI: 10.1136/jmedgenet-2012-101406. View

17.

Marini C, Conti V, Mei D, Battaglia D, Lettori D, Losito E . PRRT2 mutations in familial infantile seizures, paroxysmal dyskinesia, and hemiplegic migraine. Neurology. 2012; 79(21):2109-14. PMC: 3511926. DOI: 10.1212/WNL.0b013e3182752ca2. View

18.

Sutherland H, Albury C, Griffiths L . Advances in genetics of migraine. J Headache Pain. 2019; 20(1):72. PMC: 6734342. DOI: 10.1186/s10194-019-1017-9. View

19.

Xu Y, Padiath Q, Shapiro R, Jones C, Wu S, Saigoh N . Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature. 2005; 434(7033):640-4. DOI: 10.1038/nature03453. View

20.

Pettingill P, Weir G, Wei T, Wu Y, Flower G, Lalic T . A causal role for TRESK loss of function in migraine mechanisms. Brain. 2019; 142(12):3852-3867. PMC: 6906598. DOI: 10.1093/brain/awz342. View