Genetics of migraine.
Genetics of migraine.
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DOI：
10.1016/b978-0-444-64076-5.00031-4
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Palotie, Aarno
中科院分区：
文献类型：
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作者：
Anttila, Verneri;Wessman, Maija;Palotie, Aarno
偏头痛的遗传学最近经历了重大转变，在几年的时间里，从仅有的几个罕见孟德尔形式的已知基因转移到了47个影响常见形式偏头痛易感性的已知常见变异基因。这在很大程度上是通过迅速增加全基因组关联研究的样本大小来实现的，紧随其后的是第一波大规模外显子组测序研究。大量检测到的基因座，主要是TRPM8、PRDM16和LRP1，使得许多电子分析成为可能，这些分析揭示了偏头痛常见风险变异的功能和组织水平，包括参与血管和神经机制的证据。基于GWAS信息的多基因风险评分和其他遗传差异测量正在进一步打开剖析药物遗传学、功能病因学和合并症的大门。基于遗传性的分析表明，偏头痛和其他神经精神障碍和大脑表型之间存在密切联系，突出了偏头痛与严重抑郁障碍和注意力缺陷多动障碍等之间的遗传联系。这些最近在偏头痛遗传学方面的成功开始成熟到足以为常见偏头痛的特定可量化遗传因素提供强有力的证据。
Genetics of migraine has recently undergone a major shift, moving in the space of a few years from having only a few known genes for rare Mendelian forms to 47 known common variant loci affecting the susceptibility of the common forms of migraine. This has largely been achieved by rapidly increasing sample sizes for genomewide association studies (GWAS), soon to be followed by the first wave of large-scale exome-sequencing studies. The large number of detected loci, chief among them TRPM8, PRDM16, and LRP1, have enabled a number of in silico analyses, which have shed light on the functional and tissue-level aspects of the common risk variants for migraine, including evidence for involvement of both vascular and neuronal mechanisms. Polygenic risk scores and other measures of genetic variance based on GWAS information are further opening the door to dissecting pharmacogenetics, functional etiology, and comorbidity. Heritability-based analyses are demonstrating strong links between migraine and other neuropsychiatric disorders and brain phenotypes, highlighting genetic links between migraine and major depressive disorder and attention-deficit hyperactivity disorder, among others. These recent successes in migraine genetics are starting to be mature enough to provide robust evidence of specific quantifiable genetic factors in common migraine.