A1 Refereed original research article in a scientific journal
Genome-wide association analysis identifies susceptibility loci for migraine without aura
Authors: Freilinger T, Anttila V, de Vries B, Malik R, Kallela M, Terwindt GM, Pozo-Rosich P, Winsvold B, Nyholt DR, van Oosterhout WPJ, Artto V, Todt U, Hamalainen E, Fernandez-Morales J, Louter MA, Kaunisto MA, Schoenen J, Raitakari O, Lehtimaki T, Vila-Pueyo M, Gobel H, Wichmann E, Sintas C, Uitterlinden AG, Hofman A, Rivadeneira F, Heinze A, Tronvik E, van Duijn CM, Kaprio J, Cormand B, Wessman M, Frants RR, Meitinger T, Muller-Myhsok B, Zwart JA, Farkkila M, Macaya A, Ferrari MD, Kubisch C, Palotie A, Dichgans M, van den Maagdenberg AMJM
Publisher: NATURE PUBLISHING GROUP
Publication year: 2012
Journal: Nature Genetics
Journal name in source: NATURE GENETICS
Journal acronym: NAT GENET
Number in series: 7
Volume: 44
Issue: 7
First page : 777
Last page: 782
Number of pages: 8
ISSN: 1061-4036
DOI: https://doi.org/10.1038/ng.2307
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.
