Tummoszeit Inga Zalia, Olofsson Isa Amalie, Chalmer Mona Ameri, Henriksen Alexander Pil, Aagaard Bitten, Brunak Søren, Bruun Mie Topholm, Didriksen Maria, Erikstrup Christian, Hjalgrim Henrik, Mikkelsen Christina, Mikkelsen Susan, Ostrowski Sisse Rye, Pedersen Ole Birger Vesterager, Quinn Liam, Sørensen Erik, Ullum Henrik, Olesen Jes, Banasik Karina, Hansen Thomas Folkmann, Kogelman Lisette J A
Danish Headache Center, Department of Neurology, Copenhagen University Hospital, Glostrup, Denmark.
Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Headache. 2025 Jan;65(1):124-131. doi: 10.1111/head.14784. Epub 2024 Oct 1.
To determine the association between human leukocyte antigen (HLA) alleles and migraine, migraine subtypes, and sex-specific factors.
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.
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.
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.
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.
确定人类白细胞抗原（HLA）等位基因与偏头痛、偏头痛亚型及性别特异性因素之间的关联。
长期以来一直有人提出炎症参与偏头痛的病理生理过程。本研究检测了偏头痛与HLA系统等位基因之间的关联，HLA系统是免疫反应和遗传多样性中的关键因素。
我们开展了一项病例对照研究，纳入了13210例偏头痛患者和86738例对照。所有参与者均为丹麦献血者研究基因组队列的一部分。对参与者进行基因分型，并推算出15个HLA基因上的111个HLA等位基因。我们在考虑性别差异的情况下，检测了HLA等位基因与偏头痛亚型之间的关联。
我们发现HLA等位基因与偏头痛之间无关联，无论是总体情况还是在性别特异性分析中均如此。在偏头痛亚型分析中，有三个HLA等位基因与无先兆偏头痛相关；然而，这些关联在一个独立的冰岛队列（2191例无先兆偏头痛患者和278858例对照）中无法重复验证。此外，我们发现HLA等位基因与有先兆偏头痛或慢性偏头痛之间无关联。
我们未发现HLA系统与偏头痛之间存在关联的证据，这表明与HLA系统相关的遗传因素在偏头痛易感性中不发挥重要作用。
