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. 2024 Oct 25:15:1445649.
doi: 10.3389/fneur.2024.1445649. eCollection 2024.

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study

Jin Yang #  1   2 , Xiaoli Song #  1   2 , Lei Shi  1   2 , Shuhao Du  1   2 , Jieying Zhang  1   2 , Gang Huang  3 , Xuancheng Zhou  3 , Hao Chi  3 , Qian Zhu  1   2
Affiliations

New insights into the increased risk of migraines from COVID-19 infection and vaccination: a Mendelian randomization study

Jin Yang et al. Front Neurol. .

Abstract

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent attacks, leading to a substantial global disease burden. Recent observational studies have reported the onset and worsening of migraine following COVID-19 infection and vaccination. However, traditional observational study designs have limitations in controlling for confounding factors, potentially resulting in biased and inconsistent conclusions. To address this, we applied Mendelian randomization (MR) to investigate the causal relationship between COVID-19 infection and vaccination with migraine.

Methods: This study utilized summary-level genome-wide association study (GWAS) data from the GWAS catalog and FinnGen database to evaluate the effects of varying degrees of COVID-19 infection and vaccination on migraine. We employed inverse variance weighted (IVW) fixed-effect and random-effect models as the primary methods for MR analysis, with MR-Egger and other approaches as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept regression, and MR-PRESSO, were conducted to ensure robustness of the results.

Results: Our MR analysis revealed no significant causal association between COVID-19 infection and migraine. However, a significant causal association was found between COVID-19 vaccination and migraine (beta = 0.071, P = 0.034). The results were confirmed through a series of sensitivity tests, demonstrating the robustness of the findings.

Discussion: This study provides novel evidence of a significant causal link between COVID-19 vaccination and migraine, while no such association was observed with COVID-19 infection. These findings may have important implications for clinical practice, particularly in planning treatment adjustments and optimizing patient care for individuals with migraines in the context of COVID-19 vaccination.

Keywords: COVID-19; COVID-19 vaccination; GWAS; Mendelian randomization study; migraine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The workflow of this MR study.
Figure 2
Figure 2
Scatter plot of the estimated effects of COVID-19 related phenotypes (COVID-19 infection, hospitalized COVID-19, critically ill COVID-19 and COVID-19 vaccination) on migraine in the European population through single nucleotide polymorphisms (SNPs). Each black dot represents an individual SNP, plotted with error bars corresponding to each standard error (SE). The slope of each line corresponds to the combined estimates from methods using the weighted fixed effects model of inverse variance (light blue line), weighted random effects model of inverse variance (red line), MR-Egger (purple line), weighted median (green line), and weighted mode (yellow line). (A) COVID-19 infection; (B) hospitalized COVID-19; (C) critically ill COVID-19; (D) COVID-19 vaccination.
Figure 3
Figure 3
Forest plot of the causal SNP effects of COVID-19 related phenotypes (COVID-19 infection, hospitalized COVID-19, critically ill COVID-19 and COVID-19 vaccination) on migraine in the European population. Error bars represent the 95% confidence intervals (CI). (A) COVID-19 infection; (B) hospitalized COVID-19; (C) critically ill COVID-19; (D) COVID-19 vaccination.
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