Modifiable factors for migraine prophylaxis: A mendelian randomization analysis

Abstract

Objective: To examine the causal effect of potentially modifiable risk factors contributing to migraine pathogenesis. Methods: We performed Mendelian randomization analyses and acquired data from United Kingdom Biobank, FinnGen Biobank, and the MRC IEU OpenGWAS data infrastructure. An inverse-variance weighted (IVW) model was used to examine the relationship between 51 potentially modifiable risk factors and migraine in 3215 participants with migraine without aura (MwoA), 3541 participants with migraine with aura (MwA), and 176,107 controls. We adopted a Bonferroni-corrected threshold of p = 9.8 × 10-4 (.05 divided by 51 exposures) as a sign of significant effect, and a p < .05 was considered as the sign of a suggestive association. Results: More years of schooling significantly correlated with lower odds of MwoA pathogenesis (OR .57 [95%CI .44 to .75], p < .0001). More vitamin B12 intake (OR .49 [95%CI .24 to .99], p = .046) and lower level of stress [OR 8.17 (95%CI 1.5 to 44.36), p = .015] or anxiety disorder (OR 1.92 × 109 [95%CI 8.76 to 4.23*1017], p = .029) were suggestive to be correlated lower odds of MwoA pathogenesis. More coffee intake (OR .39 [95%CI .22 to .7], p = .001), lower level of eicosapentaenoic acid status (OR 2.54 [95%CI 1.03 to 6.26], p = .043), and more light physical activity (OR .09 [95%CI .01 to .94], p = .046) were suggestive to be associated with lower odds of MwA. Conclusion: The years of schooling, light physical activity, vitamin B12 intake, and coffee intake were the protective factors for migraine; stress, anxiety, and eicosapentaenoic acid status were harmful factors. Interventions could be developed based on modifying these factors for migraine prophylaxis.

Keywords: mendelian randomization; migraine prophylaxis; modifiable risk factors; public health; schooling.

FIGURE 1

Odds ratios for associations between genetically predicted risk factors and migraine without aura. OR, odds ratio; SNP, single nucleotide polymorphisms. Annotation: We used the inverse-variance weighted method to calculate the odds ratios for individual SNPs. The odds ratio represents the odds ratio per genetically predicted SD unit increase in the risk factor. Take alcohol intake frequency for example, one SD unit increase in alcohol intake frequency was associated with 1.21 higher odds of migraine pathogenesis, which indicates that a higher frequency of alcohol intake was associated with a higher odds of migraine pathogenesis.

FIGURE 2

Scatter plots of the association between years of schooling, vitamin B12, and stress and migraine without aura. IVW, inverse variance weighted; MR, Mendelian randomization; SNP, single nucleotide polymorphisms. Annotation: Scatter plots of the migraine-SNP associations (y-axis) versus the exposures-SNP associations (x-axis) were shown, with vertical and horizontal lines showing 95% confidence intervals. The fitted curves among the dots refer to the differential statistical analysis methods. The MR analyses were performed with the inverse variance weighted method, the MR-Egger method, the weighted median method, and the IVW radial method. (A) shows the scatter plot for years of schooling, (B) shows the level of vitamin B12, and (C) shows the stress owing to financial difficulties.

FIGURE 3

Odds ratios for associations between genetically predicted risk factors and migraine with aura. OR, odds ratio; SNP, single nucleotide polymorphisms. Annotation: We used the inverse-variance weighted method to calculate the odds ratios for individual SNPs. The odds ratio represents the odds ratio per genetically predicted SD unit increase in the risk factor.

FIGURE 4

Scatter plots of the association between coffee intake, EPA status, light physical activity and migraine with aura. EPA, Eicosapentaenoic acid; IVW, inverse variance weighted; MR, Mendelian randomization; SNP, single nucleotide polymorphisms. Annotation: Scatter plots of the migraine-SNP associations (y-axis) versus the exposures-SNP associations (x-axis) were shown, with vertical and horizontal lines showing 95% confidence intervals. The fitted curves among the dots refer to the differential statistical analysis methods. The MR analyses were performed with the inverse variance weighted method, the MR-Egger method, the weighted median method, and the IVW radial method. (A) shows the scatter plot of coffee intake, (B) shows EPA status, and (C) shows light physical activity.