Malik Rainer, Freilinger Tobias, Winsvold Bendik S, Anttila Verneri, Vander Heiden Jason, Traylor Matthew, de Vries Boukje, Holliday Elizabeth G, Terwindt Gisela M, Sturm Jonathan, Bis Joshua C, Hopewell Jemma C, Ferrari Michel D, Rannikmae Kristiina, Wessman Maija, Kallela Mikko, Kubisch Christian, Fornage Myriam, Meschia James F, Lehtimäki Terho, Sudlow Cathie, Clarke Robert, Chasman Daniel I, Mitchell Braxton D, Maguire Jane, Kaprio Jaakko, Farrall Martin, Raitakari Olli T, Kurth Tobias, Ikram M Arfan, Reiner Alex P, Longstreth W T, Rothwell Peter M, Strachan David P, Sharma Pankaj, Seshadri Sudha, Quaye Lydia, Cherkas Lynn, Schürks Markus, Rosand Jonathan, Ligthart Lannie, Boncoraglio Giorgio B, Davey Smith George, van Duijn Cornelia M, Stefansson Kari, Worrall Bradford B, Nyholt Dale R, Markus Hugh S, van den Maagdenberg Arn M J M, Cotsapas Chris, Zwart John A, Palotie Aarno, Dichgans Martin
Author affiliations are provided at the end of the article.
Neurology. 2015 May 26;84(21):2132-45. doi: 10.1212/WNL.0000000000001606. Epub 2015 May 1.
To quantify genetic overlap between migraine and ischemic stroke (IS) with respect to common genetic variation.
We applied 4 different approaches to large-scale meta-analyses of genome-wide data on migraine (23,285 cases and 95,425 controls) and IS (12,389 cases and 62,004 controls). First, we queried known genome-wide significant loci for both disorders, looking for potential overlap of signals. We then analyzed the overall shared genetic load using polygenic scores and estimated the genetic correlation between disease subtypes using data derived from these models. We further interrogated genomic regions of shared risk using analysis of covariance patterns between the 2 phenotypes using cross-phenotype spatial mapping.
We found substantial genetic overlap between migraine and IS using all 4 approaches. Migraine without aura (MO) showed much stronger overlap with IS and its subtypes than migraine with aura (MA). The strongest overlap existed between MO and large artery stroke (LAS; p = 6.4 × 10(-28) for the LAS polygenic score in MO) and between MO and cardioembolic stroke (CE; p = 2.7 × 10(-20) for the CE score in MO).
Our findings indicate shared genetic susceptibility to migraine and IS, with a particularly strong overlap between MO and both LAS and CE pointing towards shared mechanisms. Our observations on MA are consistent with a limited role of common genetic variants in this subtype.
量化偏头痛与缺血性卒中（IS）在常见基因变异方面的遗传重叠情况。
我们对偏头痛（23285例病例和95425例对照）和IS（12389例病例和62004例对照）的全基因组数据进行了大规模荟萃分析，采用了4种不同方法。首先，我们查询两种疾病已知的全基因组显著位点，寻找信号的潜在重叠。然后，我们使用多基因评分分析总体共享遗传负荷，并利用这些模型得出的数据估计疾病亚型之间的遗传相关性。我们还使用交叉表型空间映射分析两种表型之间的协方差模式，进一步探究共享风险的基因组区域。
我们使用所有4种方法均发现偏头痛与IS之间存在大量遗传重叠。无先兆偏头痛（MO）与IS及其亚型的重叠比有先兆偏头痛（MA）更强。MO与大动脉卒中（LAS；MO中LAS多基因评分的p = 6.4 × 10⁻²⁸）以及MO与心源性栓塞性卒中（CE；MO中CE评分的p = 2.7 × 10⁻²⁰）之间存在最强的重叠。
我们的研究结果表明偏头痛和IS存在共同的遗传易感性，MO与LAS和CE之间的重叠尤为强烈，指向共同的机制。我们对MA的观察结果与常见基因变异在该亚型中的作用有限一致。
