Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
Nat Genet. 2010 Oct;42(10):869-73. doi: 10.1038/ng.652. Epub 2010 Aug 29.
Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10⁻⁹, odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10⁻¹¹ (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10⁻⁵, permuted threshold for genome-wide significance 7.7 × 10⁻⁵. To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.
偏头痛是一种常见的发作性神经系统疾病，通常表现为反复发作的严重头痛和自主神经功能障碍。除了罕见的单基因亚型外，尚未有令人信服的偏头痛遗传或分子标志物被确定。我们在一项对来自三个欧洲头痛诊所的 2731 例偏头痛病例和 10747 例人群匹配对照进行的全基因组关联研究中，确定了 8q22.1 染色体上 rs1835740 的次要等位基因与偏头痛相关（P=5.38×10⁻⁹，优势比=1.23，95%CI 1.150-1.324）。该关联在 3202 例病例和 40062 例对照的总体荟萃分析中得到了复制，总体分析 P 值为 1.69×10⁻¹¹（优势比=1.18，95%CI 1.127-1.244）。rs1835740 位于 MTDH（星形细胞升高基因 1，也称为 AEG-1）和 PGCP（编码血浆谷氨酸羧肽酶）之间。在淋巴母细胞系的表达数量性状研究中，发现 MTDH 的转录水平与 rs1835740 有显著相关性（P=3.96×10⁻⁵，全基因组显著性的置换阈值为 7.7×10⁻⁵。据我们所知，我们的数据确立了 rs1835740 作为偏头痛的第一个遗传风险因素。
