BackgroundMigraine is a complex neurovascular disorder with a strong genetic component. There are rare monogenic forms of migraine, as well as more common polygenic forms; research into the genes involved in both types has provided insights into the many contributing genetic factors. This review summarises advances that have been made in the knowledge and understanding of the genes and genetic variations implicated in migraine etiology.FindingsMigraine is characterised into two main types, migraine without aura (MO) and migraine with aura (MA). Hemiplegic migraine is a rare monogenic MA subtype caused by mutations in three main genes - CACNA1A, ATP1A2 and SCN1A - which encode ion channel and transport proteins. Functional studies in cellular and animal models show that, in general, mutations result in impaired glutamatergic neurotransmission and cortical hyperexcitability, which make the brain more susceptible to cortical spreading depression, a phenomenon thought to coincide with aura symptoms. Variants in other genes encoding ion channels and solute carriers, or with roles in regulating neurotransmitters at neuronal synapses, or in vascular function, can also cause monogenic migraine, hemiplegic migraine and related disorders with overlapping symptoms. Next-generation sequencing will accelerate the finding of new potentially causal variants and genes, with high-throughput bioinformatics analysis methods and functional analysis pipelines important in prioritising, confirming and understanding the mechanisms of disease-causing variants.With respect to common migraine forms, large genome-wide association studies (GWAS) have greatly expanded our knowledge of the genes involved, emphasizing the role of both neuronal and vascular pathways. Dissecting the genetic architecture of migraine leads to greater understanding of what underpins relationships between subtypes and comorbid disorders, and may have utility in diagnosis or tailoring treatments. Further work is required to identify causal polymorphisms and the mechanism of their effect, and studies of gene expression and epigenetic factors will help bridge the genetics with migraine pathophysiology.ConclusionsThe complexity of migraine disorders is mirrored by their genetic complexity. A comprehensive knowledge of the genetic factors underpinning migraine will lead to improved understanding of molecular mechanisms and pathogenesis, to enable better diagnosis and treatments for migraine sufferers.

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偏头痛遗传学研究进展

背景偏头痛是一种复杂的神经血管疾病，具有很强的遗传成分。偏头痛有罕见的单基因形式，以及更常见的多基因形式；对涉及这两种类型的基因的研究提供了对许多促成遗传因素的见解。本综述总结了在偏头痛病因学中涉及的基因和遗传变异的知识和理解方面取得的进展。发现偏头痛分为两种主要类型，无先兆偏头痛 (MO) 和有先兆偏头痛 (MA)。偏瘫性偏头痛是一种罕见的单基因 MA 亚型，由三个主要基因——CACNA1A、ATP1A2 和 SCN1A——编码离子通道和转运蛋白的突变引起。细胞和动物模型的功能研究表明，一般来说，突变导致谷氨酸能神经传递受损和皮质过度兴奋，这使大脑更容易受到皮质扩散抑制的影响，这种现象被认为与先兆症状相吻合。编码离子通道和溶质载体的其他基因的变异，或在调节神经元突触的神经递质或血管功能方面的作用，也可能导致单基因偏头痛、偏瘫性偏头痛和相关疾病的重叠症状。下一代测序将加速发现新的潜在致病变异和基因，高通量生物信息学分析方法和功能分析管道在优先排序、确认和理解致病变异的机制方面很重要。对于常见的偏头痛形式，大型全基因组关联研究 (GWAS) 极大地扩展了我们对相关基因的了解，强调了神经元和血管通路的作用。剖析偏头痛的遗传结构可以更好地了解亚型和共病疾病之间的关系，并且可能在诊断或定制治疗中有用。需要进一步的工作来确定因果多态性及其作用机制，基因表达和表观遗传因素的研究将有助于将遗传学与偏头痛病理生理学联系起来。结论偏头痛疾病的复杂性反映在其遗传复杂性上。全面了解偏头痛的遗传因素将有助于更好地了解分子机制和发病机制，