Causal Associations of Modifiable Risk Factors With Migraine: Evidence From Mendelian Randomization Analysis

Background and objectives The exact etiology of migraine is unknown; however, it is likely a mixture of genetic and non-genetic factors including lifestyle variables like smoking and diet. This study aims to assess the causal effect of modifiable risk factors on the risk of migraine using two-sample Mendelian randomization. Materials and methods The study used publicly available genome-wide significant single nucleotide polymorphisms (SNPs). The study evaluated a diverse smoking exposure, encompassing age at smoking initiation, smoking intensity, and maternal smoking, alongside other pertinent risk factors, namely key dietary aspects, coffee consumption, BMI, and physical activity. Self-reported migraine was the outcome of the study. The genetic data for migraine were obtained from the FinnGen (Finland) and the UK Biobank (United Kingdom) cohorts. Results With sample sizes ranging from 64,949 to 632,802 for each risk factor collected from several consorts, the study included a total of 282 SNPs for all risk factors. The findings demonstrated that in the FinnGen consortium, genetically estimated dietary factors as well as BMI, were significantly associated with the risk of migraine (OR 0.765 per single unit of BMI, p = 0.011; OR 0.468 per one SD higher cheese intake, p = 0.012; OR 0.286 per one SD higher salad intake, p = 0.004, and 0.625 per one SD higher coffee consumption, p = 0.003, respectively). The results also showed that in the UK Biobank specifically, a genetically estimated history of maternal smoking was significantly associated with an elevated risk of migraine (OR=1.02, p=0.004). Conclusions The latest study implies a connection between maternal smoking and a heightened risk of migraines, whereas cheese intake, salad intake, coffee consumption, BMI, and physical activity are associated with a lower risk of migraine development.