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.