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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles


Title: Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
Author: International Headache Genetics Consortium
HUNT All-in Headache
Danish Blood Donor Study Genomic Cohort
Date: 2022-02
Language: English
Scope: 9
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Series: Nature Genetics; 54(2)
ISSN: 1061-4036
DOI: https://doi.org/10.1038/s41588-021-00990-0
Subject: Taugasjúkdómafræði; Mígreni; Genarannsóknir; Gen; Migraine Disorders; Genetic Predisposition to Disease; Genome-Wide Association Study; Genetics
URI: https://hdl.handle.net/20.500.11815/3029

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Citation:

International Headache Genetics Consortium , HUNT All-in Headache & Danish Blood Donor Study Genomic Cohort 2022 , ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ' , Nature Genetics , vol. 54 , no. 2 , pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0

Abstract:

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.

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Publisher Copyright: © 2022. The Author(s).

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