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Meta-Analysis
. 2013 Aug;45(8):912-917.
doi: 10.1038/ng.2676. Epub 2013 Jun 23.

Genome-wide Meta-Analysis Identifies New Susceptibility Loci for Migraine

Verneri Anttila #  1   2   3   4 Bendik S Winsvold #  1   5 Padhraig Gormley  1 Tobias Kurth  6   7   8 Francesco Bettella  9 George McMahon  10 Mikko Kallela  11 Rainer Malik  12 Boukje de Vries  13 Gisela Terwindt  14 Sarah E Medland  15 Unda Todt  16 Wendy L McArdle  10 Lydia Quaye  17 Markku Koiranen  18 M Arfan Ikram  19   20   21 Terho Lehtimäki  22 Anine H Stam  14 Lannie Ligthart  23   24 Juho Wedenoja  25 Ian Dunham  26 Benjamin M Neale  3   4 Priit Palta  1   2 Eija Hamalainen  1   2 Markus Schürks  27 Lynda M Rose  8 Julie E Buring  8 Paul M Ridker  8   28 Stacy Steinberg  9 Hreinn Stefansson  9 Finnbogi Jakobsson  29 Debbie A Lawlor  10 David M Evans  10 Susan M Ring  10 Markus Färkkilä  11 Ville Artto  11 Mari A Kaunisto  2   30 Tobias Freilinger  12   31 Jean Schoenen  32 Rune R Frants  13 Nadine Pelzer  14 Claudia M Weller  13 Ronald Zielman  14 Andrew C Heath  33 Pamela A F Madden  33 Grant W Montgomery  15 Nicholas G Martin  15 Guntram Borck  16 Hartmut Göbel  34 Axel Heinze  34 Katja Heinze-Kuhn  34 Frances M K Williams  17 Anna-Liisa Hartikainen  35 Anneli Pouta  18   35   36 Joyce van den Ende  19 Andre G Uitterlinden  37 Albert Hofman  38 Najaf Amin  19 Jouke-Jan Hottenga  23 Jacqueline M Vink  23 Kauko Heikkilä  25 Michael Alexander  39   40 Bertram Muller-Myhsok  41   42 Stefan Schreiber  43   44 Thomas Meitinger  45   46 Heinz Erich Wichmann  47   48   49 Arpo Aromaa  50 Johan G Eriksson  30   50   51   52   53 Bryan Traynor  54 Daniah Trabzuni  55   56 North American Brain Expression ConsortiumUK Brain Expression ConsortiumElizabeth Rossin  3   4   57 Kasper Lage  3   4   58   59   60 Suzanne B R Jacobs  4 J Raphael Gibbs  54   55 Ewan Birney  26 Jaakko Kaprio  2   61   25 Brenda W Penninx  62   24   63   64 Dorret I Boomsma  23 Cornelia van Duijn  19 Olli Raitakari  65   66 Marjo-Riitta Jarvelin  67   18   68   36 John-Anker Zwart  5 Lynn Cherkas  17 David P Strachan  69 Christian Kubisch  16 Michel D Ferrari  14 Arn M J M van den Maagdenberg  13   14 Martin Dichgans  12   42 Maija Wessman  2   30 George Davey Smith  10 Kari Stefansson  9   70 Mark J Daly  3   4 Dale R Nyholt  15 Daniel Chasman  8   28 Aarno Palotie  1   2   4
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Free PMC article
Meta-Analysis

Genome-wide Meta-Analysis Identifies New Susceptibility Loci for Migraine

Verneri Anttila et al. Nat Genet. .
Free PMC article

Abstract

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5×10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

Figures

Figure 1
Figure 1. Description of the studies comprising the International Migraine Genetics Meta-analysis Consortium, and their sample contributions to each analysis
Each coloured box corresponds to one analysed phenotype and lists the total number of cases and controls, as well as the sample contributions of individual cohorts. Participation in each analysis depended on the availability of the data in question and the recruitment method.
Figure 2
Figure 2. Manhattan plot of the results of the meta-analysis
Results of the meta-analysis of all migraine cases, of any migraine subtype or recruiting method, versus all available controls, adjusting for gender. Red dots indicate SNPs with significant (< 5 × 10−8) P values. A) All migraine (23 285 cases, 95 425 controls) B) Clinic-based studies only (5 175 cases, 13 972 controls) C) Migraine with aura (5 118 cases, 74 239 controls) D) Migraine without aura (7 107 cases, 69 427 controls)
Figure 2
Figure 2. Manhattan plot of the results of the meta-analysis
Results of the meta-analysis of all migraine cases, of any migraine subtype or recruiting method, versus all available controls, adjusting for gender. Red dots indicate SNPs with significant (< 5 × 10−8) P values. A) All migraine (23 285 cases, 95 425 controls) B) Clinic-based studies only (5 175 cases, 13 972 controls) C) Migraine with aura (5 118 cases, 74 239 controls) D) Migraine without aura (7 107 cases, 69 427 controls)
Figure 2
Figure 2. Manhattan plot of the results of the meta-analysis
Results of the meta-analysis of all migraine cases, of any migraine subtype or recruiting method, versus all available controls, adjusting for gender. Red dots indicate SNPs with significant (< 5 × 10−8) P values. A) All migraine (23 285 cases, 95 425 controls) B) Clinic-based studies only (5 175 cases, 13 972 controls) C) Migraine with aura (5 118 cases, 74 239 controls) D) Migraine without aura (7 107 cases, 69 427 controls)
Figure 2
Figure 2. Manhattan plot of the results of the meta-analysis
Results of the meta-analysis of all migraine cases, of any migraine subtype or recruiting method, versus all available controls, adjusting for gender. Red dots indicate SNPs with significant (< 5 × 10−8) P values. A) All migraine (23 285 cases, 95 425 controls) B) Clinic-based studies only (5 175 cases, 13 972 controls) C) Migraine with aura (5 118 cases, 74 239 controls) D) Migraine without aura (7 107 cases, 69 427 controls)

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