Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine
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DOI：
10.1038/ng.3598
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发表时间：
2016-08-01
期刊：
影响因子：
30.8
通讯作者：
Palotie, Aarno
中科院分区：
文献类型：
--
作者：
Gormley, Padhraig;Anttila, Verneri;Palotie, Aarno
偏头痛是一种使人衰弱的神经系统疾病，影响全球约七分之一的人，但其分子机制仍知之甚少。关于偏头痛是血管功能障碍的疾病还是神经元功能障碍伴继发性血管改变的结果，存在一些争论。全基因组关联（GWA）研究迄今已确定了13个与偏头痛相关的独立位点。为了确定新的易感基因座，我们对来自22项GWA研究的59，674名受试者和316，078名对照者进行了偏头痛的遗传研究。我们确定了44个独立的单核苷酸多态性（SNP）与偏头痛风险显著相关（P < 5 x 10（-8）），映射到38个不同的基因组位点，包括28个以前未报道的位点和一个据我们所知是第一个在X染色体上被确定的位点。在随后的计算分析中，所鉴定的位点显示血管和平滑肌组织中表达的基因富集，这与突出血管病因的偏头痛的主导理论一致。
Migraine is a debilitating neurological disorder affecting around one in seven people worldwide, but its molecular mechanisms remain poorly understood. There is some debate about whether migraine is a disease of vascular dysfunction or a result of neuronal dysfunction with secondary vascular changes. Genome-wide association ( GWA) studies have thus far identified 13 independent loci associated with migraine. To identify new susceptibility loci, we carried out a genetic study of migraine on 59,674 affected subjects and 316,078 controls from 22 GWA studies. We identified 44 independent single-nucleotide polymorphisms ( SNPs) significantly associated with migraine risk ( P < 5 x 10(-8)) that mapped to 38 distinct genomic loci, including 28 loci not previously reported and a locus that to our knowledge is the first to be identified on chromosome X. In subsequent computational analyses, the identified loci showed enrichment for genes expressed in vascular and smooth muscle tissues, consistent with a predominant theory of migraine that highlights vascular etiologies.