Department of Neurology, The Danish Headache Center, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark.
Eur J Neurol. 2013 May;20(5):765-72. doi: 10.1111/ene.12055. Epub 2013 Jan 7.
Genetic factors contribute to the aetiology of the prevalent form of migraine without aura (MO) and migraine with typical aura (MTA). Due to the complex inheritance of MO and MTA, the genetic background is still not fully established. In a population-based genome-wide association study by Chasman et al. (Nat Genet 2011: 43: 695-698), three common variants were found to confer risk of migraine at a genome-wide significant level (P < 5 × 10(-8) ). We aimed to evaluate the top association single nucleotide polymorphisms (SNPs) from the discovery set by Chasman et al. in a primarily clinic-based Danish and Icelandic cohort.
The top association SNPs were assessed in 2523 cases and 38,170 controls, and a meta-analysis was performed, combining the discovery set with all the follow-up studies. Finally the confirmed SNPs were assessed in a genotype-phenotype analysis.
Two out of three SNPs that showed genome-wide significant associations in the previous study: rs10166942 (near TRPM8) and rs11172113 (in LRP1) were significantly associated with migraine in the present study. The meta-analysis confirmed the previous three genome-wide significant associated SNPs (rs2651899, rs10166942 and rs11172113) to confer risk of migraine. In addition, the C-allele of rs2078371 (near TSPAN-2) also reached genome-wide significance for association with migraine [OR = 1.14; CI = (1.09-1.20); P = 2.55 × 10(-8) ].
TSPAN-2 encodes an integral membrane protein involved in oligodendrogenesis. This new finding supports the plausible implication of neuroglia in the pathophysiology of MO and MTA.
遗传因素导致无先兆偏头痛（MO）和有先兆偏头痛（MTA）这一常见偏头痛形式的发病。由于 MO 和 MTA 的遗传方式复杂，其遗传背景仍未完全确定。在 Chasman 等人进行的一项基于人群的全基因组关联研究中（Nat Genet 2011：43：695-698），发现三个常见变异可使偏头痛风险达到全基因组显著水平（P < 5 × 10(-8)）。我们旨在评估 Chasman 等人发现的偏头痛关联单核苷酸多态性（SNP）在丹麦和冰岛以诊所为基础的主要队列中的关联。
对 2523 例病例和 38170 例对照进行了前发现集的最高关联 SNP 评估，并进行了一项荟萃分析，将发现集与所有后续研究相结合。最终在基因型-表型分析中评估了确认的 SNP。
前一项研究中显示全基因组显著关联的三个 SNP 中的两个：rs10166942（位于 TRPM8 附近）和 rs11172113（位于 LRP1 内）在本研究中与偏头痛显著相关。荟萃分析证实了先前三个全基因组显著相关的 SNP（rs2651899、rs10166942 和 rs11172113）与偏头痛的风险相关。此外，rs2078371（位于 TSPAN-2 附近）的 C 等位基因与偏头痛也达到了全基因组显著相关[OR = 1.14；CI = （1.09-1.20）；P = 2.55 × 10(-8)]。
TSPAN-2 编码一种参与少突胶质细胞发生的整合膜蛋白。这一新发现支持神经胶质在 MO 和 MTA 病理生理学中的潜在作用。
