对37.5万人的荟萃分析确定了38个偏头痛易感基因座。
Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
作者信息
Gormley Padhraig, Anttila Verneri, Winsvold Bendik S, Palta Priit, Esko Tonu, Pers Tune H, Farh Kai-How, Cuenca-Leon Ester, Muona Mikko, Furlotte Nicholas A, Kurth Tobias, Ingason Andres, McMahon George, Ligthart Lannie, Terwindt Gisela M, Kallela Mikko, Freilinger Tobias M, Ran Caroline, Gordon Scott G, Stam Anine H, Steinberg Stacy, Borck Guntram, Koiranen Markku, Quaye Lydia, Adams Hieab H H, Lehtimäki Terho, Sarin Antti-Pekka, Wedenoja Juho, Hinds David A, Buring Julie E, Schürks Markus, Ridker Paul M, Hrafnsdottir Maria Gudlaug, Stefansson Hreinn, Ring Susan M, Hottenga Jouke-Jan, Penninx Brenda W J H, Färkkilä Markus, Artto Ville, Kaunisto Mari, Vepsäläinen Salli, Malik Rainer, Heath Andrew C, Madden Pamela A F, Martin Nicholas G, Montgomery Grant W, Kurki Mitja I, Kals Mart, Mägi Reedik, Pärn Kalle, Hämäläinen Eija, Huang Hailiang, Byrnes Andrea E, Franke Lude, Huang Jie, Stergiakouli Evie, Lee Phil H, Sandor Cynthia, Webber Caleb, Cader Zameel, Muller-Myhsok Bertram, Schreiber Stefan, Meitinger Thomas, Eriksson Johan G, Salomaa Veikko, Heikkilä Kauko, Loehrer Elizabeth, Uitterlinden Andre G, Hofman Albert, van Duijn Cornelia M, Cherkas Lynn, Pedersen Linda M, Stubhaug Audun, Nielsen Christopher S, Männikkö Minna, Mihailov Evelin, Milani Lili, Göbel Hartmut, Esserlind Ann-Louise, Christensen Anne Francke, Hansen Thomas Folkmann, Werge Thomas, Kaprio Jaakko, Aromaa Arpo J, Raitakari Olli, Ikram M Arfan, Spector Tim, Järvelin Marjo-Riitta, Metspalu Andres, Kubisch Christian, Strachan David P, Ferrari Michel D, Belin Andrea C, Dichgans Martin, Wessman Maija, van den Maagdenberg Arn M J M, Zwart John-Anker, Boomsma Dorret I, Smith George Davey, Stefansson Kari, Eriksson Nicholas, Daly Mark J, Neale Benjamin M, Olesen Jes, Chasman Daniel I, Nyholt Dale R, Palotie Aarno
机构信息
Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
出版信息
Nat Genet. 2016 Aug;48(8):856-66. doi: 10.1038/ng.3598. Epub 2016 Jun 20.
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 × 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.
偏头痛是一种使人衰弱的神经系统疾病，全球约七分之一的人受其影响，但其分子机制仍知之甚少。关于偏头痛是血管功能障碍疾病还是继发血管变化的神经元功能障碍的结果，存在一些争议。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基因座。为了确定新的易感基因座，我们对来自22项GWA研究的59674名患病受试者和316078名对照进行了偏头痛的遗传学研究。我们确定了44个与偏头痛风险显著相关（P < 5 × 10(-8)）的独立单核苷酸多态性（SNP），这些SNP定位于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首次在X染色体上确定的位点。在随后的计算分析中，所确定的位点显示在血管和平滑肌组织中表达的基因富集，这与强调血管病因的偏头痛主要理论一致。
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