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. 2025 Jan;65(1):124-131.
doi: 10.1111/head.14784. Epub 2024 Oct 1.

No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study

Inga Zalia Tummoszeit  1 , Isa Amalie Olofsson  1   2 , Mona Ameri Chalmer  1 , Alexander Pil Henriksen  3 , Bitten Aagaard  4 , Søren Brunak  3 , Mie Topholm Bruun  5 , Maria Didriksen  6   7 , Christian Erikstrup  8 , Henrik Hjalgrim  9   10   11   12 , Christina Mikkelsen  6   13 , Susan Mikkelsen  8 , Sisse Rye Ostrowski  6   9 , Ole Birger Vesterager Pedersen  9   14 , Liam Quinn  14 , Erik Sørensen  6 , Henrik Ullum  10 , Jes Olesen  1 , Karina Banasik  3   15 , Thomas Folkmann Hansen  1   3 , Lisette J A Kogelman  1   16 ; DBDS Genomic consortium group
Collaborators, Affiliations

No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study

Inga Zalia Tummoszeit et al. Headache. 2025 Jan.

Abstract

Objective: To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex-specific factors.

Background: It has long been hypothesized that inflammation contributes to migraine pathophysiology. This study examined the association between migraine and alleles in the HLA system, a key player in immune response and genetic diversity.

Methods: We performed a case-control study and included 13,210 individuals with migraine and 86,738 controls. All participants were part of the Danish Blood Donor Study Genomic Cohort. Participants were genotyped and 111 HLA alleles on 15 HLA genes were imputed. We examined the association between HLA alleles and migraine subtypes, considering sex-specific differences.

Results: We found no association between HLA alleles and migraine, neither overall, nor in the sex-specific analysis. In the migraine subtype analysis, three HLA alleles were associated with migraine without aura; however, these associations could not be replicated in an independent Icelandic cohort (2191 individuals with migraine without aura and 278,858 controls). Furthermore, we found no association between HLA alleles and migraine with aura or chronic migraine.

Conclusion: We found no evidence of an association between the HLA system and migraine, suggesting that genetic factors related to the HLA system do not play a significant role in migraine susceptibility.

Keywords: human genetics; human leukocyte antigens; major histocompatibility complex; migraine; migraine with aura; migraine without aura.

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Conflict of interest statement

Inga Zalia Tummoszeit declares no conflicts. Isa Amalie Olofsson declares no conflicts. Mona Ameri Chalmer declares no conflicts. Alexander Pil Henriksen declares no conflicts. Bitten Aagaard declares no conflicts. Søren Brunak declares no conflicts. Mie Topholm Bruun declares no conflicts. Maria Didriksen declares no conflicts. Christian Erikstrup declares no conflicts. Henrik Hjalgrim declares no conflicts. Christina Mikkelsen declares no conflicts. Susan Mikkelsen declares no conflicts. Sisse Rye Ostrowski declares no conflicts. Ole Birger Vesterager Pedersen declares no conflicts. Liam Quinn declares no conflicts. Erik Sørensen declares no conflicts. Henrik Ullum declares no conflicts. DBDS Genomic Consortium declares no conflicts. Jes Olesen declares no conflicts. Karina Banasik declares no conflicts. Thomas Folkmann Hansen declares no conflicts. Lisette J.A. Kogelman declares no conflicts.

Figures

FIGURE 1
FIGURE 1
Flow chart of the inclusion of participants with migraine based on either questionnaire (DaMP) or prescription history. DaMP, Danish Migraine Population; DBDS, Danish Blood Donor Study. [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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