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

Sutherland, Heidi G; Jenkins, Bronwyn; Griffiths, Lyn R

doi:10.1016/s1474-4422(24)00026-7

Cited by 9 publications

(5 citation statements)

References 133 publications

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“…In addition to the FHM genes, other genes with roles in neuronal excitability have been associated with familial migraine-related disorders [ 20 , 21 ]. For example, pathogenic variants in PRRT2 , which are commonly involved in movement disorders, have also been found in hemiplegic migraine families and cases [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene SLC1A3 Associated with Reduced Migraine Risk

Albury,

Sutherland,

Lam

et al. 2024

Genes

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Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: SLC4A4, SLC1A3, and CHRNA4. Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case–control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 (p = 0.04) and rs16903247 (p = 0.05) genotypes within the SLC1A3 gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings—rs3776578 (p = 0.0041) and rs16903247 (p = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of SLC1A3. The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of SLC1A3.

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Section: Introductionmentioning

confidence: 99%

“…A migraine is a complex neurological disorder with both rare monogenic and more common polygenic forms [ 21 ]. With respect to the latter, over 180 susceptibility variants for a migraine have now been identified, largely via genome-wide association studies (GWASs) with increasingly larger and diverse population samples [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene SLC1A3 Associated with Reduced Migraine Risk

Albury,

Sutherland,

Lam

et al. 2024

Genes

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“…As migraine is often hereditary (heritability of 30%–60%), genetics is considered vital in its pathogenesis. 1 The authors of this article conducted a GWAS in patients with migraine disorder based on their clinical and familial history. 2 The study population comprised 1,561 individuals with migraine and 473 without from a Taiwanese tertiary institution.…”

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confidence: 99%

“…Mendelian migraine disorders, typically known as familial hemiplegic migraine, are primarily monogenic and rare, and caused by mutations in genes such as CACNA1A , ATP1A2 , and SCN1A . 1 However, non-Mendelian migraine is more common, and exhibits a polygenic architecture with multiple gene variations that contribute to susceptibility. 1 GWASs have recently contributed to delineating the polygenic architecture of several diseases.…”

mentioning

confidence: 99%

“… 1 However, non-Mendelian migraine is more common, and exhibits a polygenic architecture with multiple gene variations that contribute to susceptibility. 1 GWASs have recently contributed to delineating the polygenic architecture of several diseases. Two large-scale GWAS meta-analyses in 2022 and 2023 revealed more than 100 loci associated with migraine disorder; however, a subgroup analysis was not conducted on familial history.…”

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confidence: 99%

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