Hautakangas, H., Winsvold, B.S., Ruotsalainen, S.E. et al. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat Genet 54, 152–160 (2022). https://doi.org/10.1038/s41588-021-00990-0
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
|Author:||Hautakangas, Heidi1; Winsvold, Bendik S.2,3,4; Ruotsalainen, Sanni E.1;|
1Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.
2Oslo Univ Hosp, Dept Res Innovat & Educ, Div Clin Neurosci, Oslo, Norway.
3Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, KG Jebsen Ctr Genet Epidemiol, Dept Publ Hlth & Nursing, Trondheim, Norway.
4Oslo Univ Hosp, Dept Neurol, Oslo, Norway.
5deCODE Genet Amgen Inc, Reykjavik, Iceland.
6Leiden Univ, Dept Neurol, Med Ctr, Leiden, Netherlands.
7Leiden Univ, Dept Human Genet, Med Ctr, Leiden, Netherlands.
8Copenhagen Univ Hosp, Danish Headache Ctr, Dept Neurol, Copenhagen, Denmark.
9Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway.
10Norwegian Univ Sci & Technol, BioCore Bioinformat Core Facil, Trondheim, Norway.
11Trondheim Reg & Univ Hosp, Clin Lab Med, St Olavs Hosp, Trondheim, Norway.
12Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
13GlaxoSmithKline, Cambridge, MA USA.
14Helsinki Univ Cent Hosp, Dept Neurol, Helsinki, Finland.
15Univ Copenhagen, Novo Nordic Fdn Ctr Prot Res, Copenhagen, Denmark.
16Laeknasetrid, Neurol Private Practice, Reykjavik, Iceland.
17Vrije Univ, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands.
18Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Copenhagen, Denmark.
19Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
20Harvard Med Sch, Boston, MA 02115 USA.
21Ludwig Maximilians Univ Munchen, Inst Stroke & Dementia Res, Univ Hosp, Munich, Germany.
22Munich Cluster Syst Neurol Synergy, Munich, Germany.
23Aarhus Univ Hosp, Dept Clin Immunol, Aarhus, Denmark.
24Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
25Norwegian Univ Sci & Technol NTNU, Fac Med & Hlth Sci, Dept Neuromed & Movement Sci, Trondheim, Norway.
26St Olavs Univ Hosp, Clin Res Unit Cent Norway, Trondheim, Norway.
27Landspitali Univ Hosp, Reykjavik, Iceland.
28Norwegian Univ Sci & Technol, Fac Med & Hlth Sci, HUNT Res Ctr, Dept Publ Hlth & Nursing, Trondheim, Norway.
29Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway.
30Oslo Univ Hosp, Dept Res Innovat & Educ, Div Clin Neurosci, Res & Commun Unit Musculoskeletal Hlth FORMI, Oslo, Norway.
31Tampere Univ, Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.
32Tampere Univ, Fac Med & Hlth Technol, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
33Univ Oslo, Inst Hlth & Soc, Dept Gen Practice, Oslo, Norway.
34Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway.
35Charit Univ Med Berlin, Inst Publ Hlth, Berlin, Germany.
36Tampere Univ, Fac Med & Hlth Technol, Fimlab Labs, Dept Clin Chem, Tampere, Finland.
37Zealand Univ Hosp, Dept Clin Immunol, Koge, Denmark.
38Vrije Univ, Amsterdam Publ Hlth Res Inst, Dept Psychiat, Amsterdam UMC, Amsterdam, Netherlands.
39GGZ inGeest Specialized Mental Hlth Care, Amsterdam, Netherlands.
40Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
41Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
42Leiden Univ, Dept Internal Med, Div Endocrinol, Med Ctr, Leiden, Netherlands.
43Natl Publ Hlth Inst, Finnish Inst Hlth & Welf THL, Helsinki, Finland.
44Klinikum Passau, Dept Neurol, Passau, Germany.
45Hertie Inst Clin Brain Res, Ctr Neurol, Tubingen, Germany.
46Imperial Coll London, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
47Univ Oulu, Fac Med, Ctr Life Course Hlth Res, Oulu, Finland.
48Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland.
49Brunel Univ London, Coll Hlth & Life Sci, Dept Life Sci, London, England.
50Univ Turku, Ctr Populat Hlth Res, Turku, Finland.
51Turku Univ Hosp, Turku, Finland.
52Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
53Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
54Folkhalsan Res Ctr, Helsinki, Finland.
55Queensland Univ Technol, Fac Hlth, Sch Biomed Sci, Brisbane, Qld, Australia.
56Queensland Univ Technol, Fac Hlth, Ctr Genom & Personalised Hlth, Brisbane, Qld, Australia.
57Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.
58Massachusetts Gen Hosp, Dept Med, Dept Neurol, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
59Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
60Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
61Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
62Univ Helsinki, Dept Math & Stat, Helsinki, Finland.
|Online Access:||PDF Full Text (PDF, 3.8 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2022110764859
|Publish Date:|| 2022-11-07
Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
|Pages:||152 - 160|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
3124 Neurology and psychiatry
We thank the study participants for their contribution to this research. We also thank the numerous individuals who contributed to sample collection, storage, handling, phenotyping and genotyping for each of the individual cohorts. We acknowledge the participants and investigators of the FinnGen study. This research has been conducted using the UK Biobank Resource under Application Number 22627. We are supported by following grants: the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health innovation fund Sitra and Finska Lakaresallskapet (E.W.), the Academy of Finland (grant nos. 288509, 312076, 336825 (M.P.)), the Sigrid Juselius Foundation (M.P. and S.R.), the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312062 (S.R.)), the Finnish Foundation for Cardiovascular Research (S.R.), University of Helsinki HiLIFE Fellow and Grand Challenge grants (S.R.), The Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594 (T.F.H. and K.B.)), CANDY foundation (CEHEAD) (T.F.H.), and the South-Eastern Norway Regional Health Authority (grant no. 2020034 (B.S.W.)). A list of study-specific acknowledgements and funding information can be found in the Supplementary Note.
Results for 8,117 genome-wide significant SNP associations (P < 5 × 10⁻⁸) from the meta-analysis including 23andMe data are available on the International Headache Genetics Consortium website (http://www.headachegenetics.org/content/datasets-and-cohorts). Genome-wide summary statistics for the other study collections except 23andMe are available for bona fide researchers (contact Dale Nyholt, firstname.lastname@example.org) within 2 weeks from the request. The full GWAS summary statistics for the 23andMe discovery data set will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. Please visit https://research.23andme.com/collaborate/#publication for more information and to apply to access the data.
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