Genetics of migraine: where are we now?

Grangeon, Lou; Lange, Kristin Sophie; Waliszewska‐Prosół, Marta; Onan, Dilara; Marschollek, Karol; Wiels, Wietse; Mikulenka, Petr; Farham, Fatemeh; Gollion, Cédric; Ducros, Anne

doi:10.1186/s10194-023-01547-8

Cited by 48 publications

(40 citation statements)

References 191 publications

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“…Migraine is predominant in females, peaks in productive age, and is a leading cause of disability among adults [4]. This complex condition is linked to genetic predisposition [5] and is affected by environmental factors [6]. A hyperresponsive brain, together with alterations in peripheral and central sensory processing, are proposed to underlie migraine [7] and its manifestation [8,9].…”

Section: Migrainementioning

confidence: 99%

Diet and migraine: what is proven?

Gazerani

2023

Current Opinion in Neurology

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Purpose of review The purpose of this review is to present the latest research findings about diet and migraine, what can be used in the clinic now, and what needs further investigation. Recent findings Recent findings highlight that dietary triggers exist for migraine, for example, coffee and alcohol, according to a new systematic review. Elimination diets must be personalized to delineate a balanced diet with acceptable quality and pattern. A piece of average-quality evidence shows that the ketogenic diet (KD) and the Dietary Approaches to Stop Hypertension (DASH) are effective in reducing the frequency, duration, and severity of migraine headaches in adult patients. The gut microbiome is altered in patients with migraine, and further research will identify the benefits of pre and probiotic use for migraine. Advanced digital technology in continuous monitoring can provide educational content based on patients’ needs, help patients adhere to dietary plans, and strengthen personalized care. The complex interaction of lifestyle factors, the influence of age and sex, and patients’ needs in various life phases are essential in formulating dietary plans. Summary The diet-migraine interaction is a dynamic bidirectional phenomenon that requires careful monitoring, review, and justification of dietary choices to yield the optimal outcome while minimizing potential risks.

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Section: Migrainementioning

confidence: 99%

Diet and migraine: what is proven?

Gazerani

2023

Current Opinion in Neurology

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“…A recent cross-sectional study found that MDD was strongly associated with the frequency and severity of attacks of migraine with aura, a subtype of migraine (11). Furthermore, in genetics, the importance of shared genetic factors between migraine and depression has been acknowledged (12). Although MDD and migraine are frequently seen together, their connection has not been thoroughly established.…”

Section: Introductionmentioning

confidence: 99%

The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study

Tang

et al. 2023

Front. Neurol.

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BackgroundPrevious epidemiological and other studies have shown an association between major depressive disorder (MDD) and migraine. However, the causal relationship between them remains unclear. Therefore, this study aimed to investigate the causal relationship between MDD and migraine using a bidirectional, two-sample Mendelian randomization (MR) approach.MethodsData on MDD and migraine, including subtypes with aura migraine (MA) and without aura migraine (MO), were gathered from a publicly available genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) utilized as instrumental variables (IVs) were then screened by adjusting the intensity of the connection and removing linkage disequilibrium. To explore causal effects, inverse variance weighting (IVW) was used as the primary analysis method, with weighted median, MR-Egger, simple mode, and weighted mode used as supplementary analytic methods. Furthermore, heterogeneity and pleiotropy tests were carried out. Cochran’s Q-test with IVW and MR-Egger was used to assess heterogeneity. Pleiotropy testing was carried out using the MR-Egger intercept and MR-PRESSO analysis methods. A leave-one-out analysis was also used to evaluate the stability of the findings. Finally, we used migraine (MA and MO) levels to deduce reverse causality with MDD risk.ResultsRandom effects IVW results were (MDD-Migraine: odds ratio (OR), 1.606, 95% confidence interval (CI), 1.324–1.949, p = 1.52E-06; MDD-MA: OR, 1.400, 95%CI, 1.067–1.8378, p = 0.015; MDD-MO: OR, 1.814, 95%CI, 1.277–2.578, p = 0.0008), indicating a causal relationship between MDD levels and increased risk of migraine (including MA and MO). In the inverse MR analysis, the findings were all negative, while in sensitivity analyses, the results were robust except for the study of MA with MDD.ConclusionOur study confirms a causal relationship between MDD levels and increased risk of migraine, MA, and MO. There was little evidence in the reverse MR analysis to suggest a causal genetic relationship between migraine (MA and MO) and MDD risk levels.

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“…FHM is most often an autosomal dominant trait [5]. The three rst identi ed genes all encode ion channels or transporters.…”

Section: Introductionmentioning

confidence: 99%

“…CACNA1A on 19p13 (FHM1-MIM 301011) encodes the pore-forming subunit of neuronal voltage-gated calcium channels Ca V 2.1; ATP1A2 on1q23 (FHM2 -MIM 182340) encodes the catalytic subunit of a sodium/potassium ATP-dependent pump mainly expressed in astrocytes, and SCN1A on 2q24 (FHM3 -MIM 182389) codes for the pore-forming subunit of neuronal voltage-gated sodium channels Na V 1.1. [3,5]. Study of murine models have shown that FHM variants in CACNA1A, ATP1A2 and SCN1A facilitated the initiation of cortical spreading depression waves, the surrogate of migraine aura [5].…”

Section: Introductionmentioning

confidence: 99%

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Pathogenic SCN2A variants are associated with familial and sporadic hemiplegic migraine

Riant,

Thompson,

DeKeyser

et al. 2023

Preprint

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Background: Familial hemiplegic migraine is a severe autosomal dominant subtype of migraine with aura characterized by transient motor weakness during attacks. Previously identified genes CACNA1A, ATP1A2, SCN1A and PRRT2 account for less than 20% of cases with hemiplegic migraine referred for genetic diagnosis. Objectives and Methods: To identify a novel gene, we conducted a whole-genome linkage analysis combined with mini-exome sequencing in a four-generation pedigree with hemiplegic migraine. A candidate ion channel gene was analyzed for mutations in six other affected pedigrees comprising at least three available affected members, and in a large panel of unrelated probands with hemiplegic migraine referred for molecular diagnosis, all without mutations in the known genes. The functional consequences of the identified variants were determined. Results: In the discovery pedigree, we identified a heterozygous missense mutation (c.4438A>G, p.Lys1480Glu) in the neuronal voltage-gated sodium channel gene SCN2A, which cosegregated with the hemiplegic migraine phenotype. We detected another mutation (c.769T>A, p.Phe257Ile) cosegregating with hemiplegic migraine in a second family, in which two members also had infantile seizures. A third variant (c.3955C>G, p.Arg1319Gly) was found in a sporadic hemiplegic migraine case. All three SCN2A variants were absent in the genome aggregation database gnomAD. Heterologous expression in HEK293T cells coupled with automated patch clamp recording demonstrated abnormal voltage-dependent and kinetic properties of all three SCN2A variants. Conclusions:Dysfunction of the neuronal sodium channel SCN2A can be associated with familial and sporadic hemiplegic migraine. Our finding expands the genetic landscape for migraine and contributes to the diverse genotype-phenotype spectrum associated with SCN2A.

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Genetics of migraine: where are we now?

Cited by 48 publications

References 191 publications

Diet and migraine: what is proven?

Diet and migraine: what is proven?

The relationship between major depression and migraine: A bidirectional two-sample Mendelian randomization study

Pathogenic SCN2A variants are associated with familial and sporadic hemiplegic migraine

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