1. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- Author
-
Hautakangas, H., Winsvold, B.S., Ruotsalainen, S.E., Bjornsdottir, G., Harder, A.V.E., Kogelman, L.J.A., Thomas, L.F., Noordam, R., Benner, C., Gormley, P., Artto, V., Banasik, K., Bjornsdottir, A., Boomsma, D.I., Brumpton, B., Burgdorf, K.S., Buring, J.E., Chalmer, M.A., Boer, I. de, Dichgans, M., Erikstrup, C., Farkkila, M., Garbrielsen, M.E., Ghanbari, M., Hagen, K., Happola, P., Hottenga, J.J., Hrafnsdottir, M.G., Hveem, K., Johnsen, M.B., Kahonen, M., Kristoffersen, E.S., Kurth, T., Lehtimaki, T., Lighart, L., Magnusson, S.H., Malik, R., Pedersen, O.B., Pelzer, N., Penninx, B.W.J.H., Ran, C., Ridker, P.M., Rosendaal, F.R., Sigurdardottir, G.R., Skogholt, A.H., Sveinsson, O.A., Thorgeirsson, T.E., Ullum, H., Vijfhuizen, L.S., Widen, E., Dijk, K.W. van, Aromaa, A., Belin, A.C., Freilinger, T., Ikram, M.A., Jarvelin, M.R., Raitakari, O.T., Terwindt, G.M., Kallela, M., Wessman, M., Olesen, J., Chasman, D.I., Nyholt, D.R., Stefansson, H., Stefansson, K., Maagdenberg, A.M.J.M. van den, Hansen, T.F., Ripatti, S., Zwart, J.A., Palotie, A., Pirinen, M., Int Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic C, Biological Psychology, APH - Mental Health, APH - Methodology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Sociology and Social Gerontology, Institute for Molecular Medicine Finland, Statistical and population genetics, Complex Disease Genetics, Clinicum, HUS Helsinki and Uusimaa Hospital District, HUS Neurocenter, Neurologian yksikkö, Genomics of Neurological and Neuropsychiatric Disorders, Centre of Excellence in Complex Disease Genetics, Genomic Discoveries and Clinical Translation, Biosciences, Faculty Common Matters (Faculty of Social Sciences), Department of Public Health, Biostatistics Helsinki, Research Programs Unit, Research Programme of Molecular Medicine, Department of Mathematics and Statistics, Helsinki Institute for Information Technology, Tampere University, Department of Clinical Physiology and Nuclear Medicine, Clinical Medicine, Department of Clinical Chemistry, Epidemiology, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and APH - Digital Health
- Subjects
Central Nervous System ,SUSCEPTIBILITY LOCI ,Migraine Disorders ,Migraine with Aura ,Quantitative Trait Loci ,PATHOPHYSIOLOGY ,Genome-wide association studies ,Cardiovascular System ,Polymorphism, Single Nucleotide ,Genetics ,Humans ,Genetic Predisposition to Disease ,TRANSCRIPTOME ,AURA ,Migraine ,Alleles ,METAANALYSIS ,GENE-EXPRESSION ,ARCHITECTURE ,MUTATIONS ,HERITABILITY ,1184 Genetics, developmental biology, physiology ,Molecular Sequence Annotation ,ASSOCIATION ,3142 Public health care science, environmental and occupational health ,Genetic Loci ,Case-Control Studies ,3111 Biomedicine ,Genome-Wide Association Study - Abstract
Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants. 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.
- Published
- 2022
- Full Text
- View/download PDF