Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine.
Padhraig GormleyVerneri AnttilaBendik S WinsvoldPriit PaltaTõnu EskoTune H PersKai-How FarhEster Cuenca-LeonMikko MuonaNicholas A FurlotteTobias KurthAndres IngasonGeorge McMahonLannie LigthartGisela M TerwindtMikko KallelaTobias M FreilingerCaroline RanScott G GordonAnine H StamStacy SteinbergGuntram BorckMarkku KoiranenLydia QuayeHieab H H AdamsTerho LehtimäkiAntti-Pekka SarinJuho WedenojaDavid A HindsJulie E BuringMarkus SchürksPaul M RidkerMaria Gudlaug HrafnsdottirHreinn StefanssonSusan M RingJouke-Jan HottengaBrenda W J H PenninxMarkus FärkkiläVille ArttoMari KaunistoSalli VepsäläinenRainer MalikAndrew C HeathPamela A F MaddenNicholas G MartinGrant W MontgomeryMitja I KurkiMart KalsReedik MägiKalle PärnEija HämäläinenHailiang HuangAndrea E ByrnesLude H FrankeJie HuangEvie StergiakouliPhil H LeeCynthia SandorCaleb WebberZameel CaderBertram Muller-MyhsokStefan SchreiberThomas MeitingerJohan G ErikssonVeikko SalomaaKauko HeikkiläElizabeth LoehrerAndre G UitterlindenAlbert HofmanCornelia M van DuijnLynn CherkasLinda M PedersenAudun StubhaugChristopher Sievert NielsenMinna MännikköEvelin MihailovLili A MilaniHartmut GöbelAnn-Louise EsserlindAnne Francke ChristensenThomas Folkmann HansenThomas Wergenull nullJaakko A KaprioArpo J AromaaOlli RaitakariMohammad Arfan IkramTim SpectorMarjo-Riitta JärvelinAndres MetspaluChristian KubischDavid P StrachanMichel D FerrariAndrea C BelinMartin DichgansMaija WessmanArn M J M van den MaagdenbergJohn-Anker ZwartDorret I BoomsmaGeorge Davey SmithKari StefanssonNicholas ErikssonMark J DalyBenjamin M NealeJes OlesenDaniel I ChasmanDale R NyholtAarno PalotiePublished in: Nature genetics (2016)
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.