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; Isa Amalie Olofsson; Mona Ameri Chalmer; Alexander Pil Henriksen; Bitten Aagaard; Søren Brunak; Mie Topholm Bruun; Maria Didriksen; Christian Erikstrup; Henrik Hjalgrim; Christina Mikkelsen; Susan Mikkelsen; Sisse Rye Ostrowski; Ole Birger Vesterager Pedersen; Liam James Elgaard Quinn; Erik Sørensen; Henrik Ullum; Jes Olesen; Karina Banasik; Thomas Folkmann Hansen; Lisette J.A. Kogelman; the DBDS Genomic consortium group

doi:10.1111/head.14784

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, Isa Amalie Olofsson, Mona Ameri Chalmer, Alexander Pil Henriksen, Bitten Aagaard, Søren Brunak, Mie Topholm Bruun, Maria Didriksen, Christian Erikstrup, Henrik Hjalgrim, Christina Mikkelsen, Susan Mikkelsen, Sisse Rye Ostrowski, Ole Birger Vesterager Pedersen, Liam James Elgaard Quinn, Erik Sørensen, Henrik Ullum, Jes Olesen, Karina Banasik, Thomas Folkmann HansenLisette J.A. Kogelman^*, the DBDS Genomic consortium group

^*Corresponding author for this work

Department of Clinical Medicine - Department of Clinical Immunology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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.

Original language	English
Journal	Headache
Volume	65
Issue	1
Pages (from-to)	124-131
Number of pages	8
ISSN	0017-8748
DOIs	https://doi.org/10.1111/head.14784
Publication status	Published - Jan 2025

Keywords

human genetics
human leukocyte antigens
major histocompatibility complex
migraine
migraine with aura
migraine without aura

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10.1111/head.14784Licence: CC BY-NC

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Tummoszeit, I. Z., Olofsson, I. A., Chalmer, M. A., Henriksen, A. P., Aagaard, B., Brunak, S., Bruun, M. T., Didriksen, M., Erikstrup, C., Hjalgrim, H., Mikkelsen, C., Mikkelsen, S., Ostrowski, S. R., Pedersen, O. B. V., Quinn, L. J. E., Sørensen, E., Ullum, H., Olesen, J., Banasik, K., ... the DBDS Genomic consortium group (2025). No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study. Headache, 65(1), 124-131. https://doi.org/10.1111/head.14784

@article{ed9999bf390a44719679b0f50b815d2c,

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

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",

author = "Tummoszeit, {Inga Zalia} and Olofsson, {Isa Amalie} and Chalmer, {Mona Ameri} and Henriksen, {Alexander Pil} and Bitten Aagaard and S{\o}ren Brunak and Bruun, {Mie Topholm} and Maria Didriksen and Christian Erikstrup and Henrik Hjalgrim and Christina Mikkelsen and Susan Mikkelsen and Ostrowski, {Sisse Rye} and Pedersen, {Ole Birger Vesterager} and Quinn, {Liam James Elgaard} and Erik S{\o}rensen and Henrik Ullum and Jes Olesen and Karina Banasik and Hansen, {Thomas Folkmann} and Kogelman, {Lisette J.A.} and Karina Banasik and Jakob Bay and Boldsen, {Jens Kj{\ae}rgaard} and Thorsten Brodersen and S{\o}ren Brunak and Demur, {Alfonso Buil} and Christoffersen, {Lea Arregui Nordahl} and Maria Didriksen and Dinh, {Khoa Manh} and Joseph Dowsett and Bjarke Feenstra and Frank Geller and Daniel Gudbjartsson and Henrik Hjalgrim and {von Stemann}, {Jakob Hjorth} and Schork, {Andrew Joseph} and Kathrine Kaspersen and Kjerulff, {Bertram Dalskov} and {the DBDS Genomic consortium group}",

year = "2025",

month = jan,

doi = "10.1111/head.14784",

language = "English",

volume = "65",

pages = "124--131",

journal = "Headache",

issn = "0017-8748",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "1",

}

Tummoszeit, IZ, Olofsson, IA, Chalmer, MA, Henriksen, AP, Aagaard, B, Brunak, S, Bruun, MT, Didriksen, M, Erikstrup, C, Hjalgrim, H, Mikkelsen, C, Mikkelsen, S, Ostrowski, SR, Pedersen, OBV, Quinn, LJE, Sørensen, E, Ullum, H, Olesen, J, Banasik, K, Hansen, TF, Kogelman, LJA & the DBDS Genomic consortium group 2025, 'No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study', Headache, vol. 65, no. 1, pp. 124-131. https://doi.org/10.1111/head.14784

No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study. / Tummoszeit, Inga Zalia; Olofsson, Isa Amalie; Chalmer, Mona Ameri et al.
In: Headache, Vol. 65, No. 1, 01.2025, p. 124-131.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - No association between migraine and HLA alleles in a cohort of 13,210 individuals with migraine from the Danish Blood Donor Study

AU - Tummoszeit, Inga Zalia

AU - Olofsson, Isa Amalie

AU - Chalmer, Mona Ameri

AU - Henriksen, Alexander Pil

AU - Aagaard, Bitten

AU - Brunak, Søren

AU - Bruun, Mie Topholm

AU - Didriksen, Maria

AU - Erikstrup, Christian

AU - Hjalgrim, Henrik

AU - Mikkelsen, Christina

AU - Mikkelsen, Susan

AU - Ostrowski, Sisse Rye

AU - Pedersen, Ole Birger Vesterager

AU - Quinn, Liam James Elgaard

AU - Sørensen, Erik

AU - Ullum, Henrik

AU - Olesen, Jes

AU - Banasik, Karina

AU - Hansen, Thomas Folkmann

AU - Kogelman, Lisette J.A.

AU - Banasik, Karina

AU - Bay, Jakob

AU - Boldsen, Jens Kjærgaard

AU - Brodersen, Thorsten

AU - Brunak, Søren

AU - Demur, Alfonso Buil

AU - Christoffersen, Lea Arregui Nordahl

AU - Didriksen, Maria

AU - Dinh, Khoa Manh

AU - Dowsett, Joseph

AU - Feenstra, Bjarke

AU - Geller, Frank

AU - Gudbjartsson, Daniel

AU - Hjalgrim, Henrik

AU - von Stemann, Jakob Hjorth

AU - Schork, Andrew Joseph

AU - Kaspersen, Kathrine

AU - Kjerulff, Bertram Dalskov

AU - the DBDS Genomic consortium group

PY - 2025/1

Y1 - 2025/1

N2 - 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.

AB - 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.

KW - human genetics

KW - human leukocyte antigens

KW - major histocompatibility complex

KW - migraine

KW - migraine with aura

KW - migraine without aura

UR - http://www.scopus.com/inward/record.url?scp=85205520467&partnerID=8YFLogxK

U2 - 10.1111/head.14784

DO - 10.1111/head.14784

M3 - Journal article

C2 - 39352055

AN - SCOPUS:85205520467

SN - 0017-8748

VL - 65

SP - 124

EP - 131

JO - Headache

JF - Headache

IS - 1

ER -

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

Abstract

Keywords

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