A replication study of GWAS findings in migraine identifies association in a Swedish case-control sample.
A replication study of GWAS findings in migraine identifies association in a Swedish case-control sample.
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DOI：
10.1186/1471-2350-15-38
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发表时间：
2014-03-28
影响因子：
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通讯作者：
Belin AC
中科院分区：
文献类型：
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作者：
Ran C;Graae L;Magnusson PK;Pedersen NL;Olson L;Belin AC
偏头痛是一种常见的神经血管疾病，症状包括中度至重度头痛和反复发作。今天没有治疗偏头痛的方法，并且对病理学知之甚少。常见形式的偏头痛具有复杂的遗传背景，遗传率估计约为50%。最近对欧洲和美国偏头痛队列的全基因组关联研究（GWAS）已经确定了偏头痛的新遗传危险因素。我们在一个瑞典人群队列中进行了一项关联研究，使用现有的阵列数据（Illumina Omni Express芯片），调查了最近在三个GWAS中被确定为偏头痛遗传风险因素的八个单核苷酸多态性（SNP）的频率。8个SNPs分别为rs2651899、rs3790455、rs10166942、rs7640543、rs9349379、rs1835740、rs6478241和rs11172113。由于无法直接获得rs3790455、rs10166942和rs7640543的信息，我们选择了与这三个SNP高度连锁不平衡（LD）的SNP，并分别用rs2274316、rs1003540和rs4075749替换。我们能够复制与rs2651899的关联，并在我们的瑞典队列中发现与rs1835740关联的趋势。这是第一个报道的瑞典偏头痛病例对照材料的遗传关联研究。因此，我们在一个独立的遗传物质中复制了偏头痛易感基因位点的发现，从而增加了对这种常见神经系统疾病遗传风险因素的了解。
Migraine is a common neurovascular disorder with symptoms including headache of moderate to severe intensity and recurring attacks. There is no cure for migraine today and the pathology is poorly understood. Common forms of migraine have a complex genetic background and heritability has been estimated to be around 50%. Recent genome-wide association studies (GWAS) on European and American migraine cohorts have led to the identification of new genetic risk factors for migraine. We performed an association study in a Swedish population based cohort, investigating the frequency of eight single nucleotide polymorphisms (SNPs) recently identified as genetic risk factors for migraine in three GWAS, using available array data (Illumina Omni Express chip). The eight SNPs were rs2651899, rs3790455, rs10166942, rs7640543, rs9349379, rs1835740, rs6478241 and rs11172113. Because information on rs3790455, rs10166942 and rs7640543 was not directly available, we selected SNPs in high Linkage Disequilibrium (LD) with these three SNPs, and replaced them with rs2274316, rs1003540 and rs4075749, respectively. We were able to replicate the association with rs2651899 and found a trend for association with rs1835740 in our Swedish cohort. This is the first reported genetic association study of a Swedish migraine case control material. We have thus replicated findings of susceptibility loci for migraine in an independent genetic material, thereby increasing knowledge about genetic risk factors for this common neurological disorder.