Although numerous studies have identified associations between socioeconomic, behavioral, dietary, and physical factors and migraine, the causal nature of these relationships has yet to be adequately established. We utilized two-sample Mendelian randomization to elucidate the causal associations of 28 distinct traits for socioeconomic factor, behavioral factor, dietary factor and physical measurement with migraine. In the univariable Mendelian randomization analysis, the inverse-variance weighted method served as the primary analytic approach. Robustness checks included Cochran Q test, Egger intercept test, and leave-one-out analysis. A multivariable Mendelian randomization analysis framework was utilized to assess the direct causal impacts of these traits on migraine risk. The univariable Mendelian randomization analysis analysis revealed that genetic predispositions to higher coffee intake (OR=0.547; 95% CI=0.359-0.834; P=0.005), greater oily fish intake (OR=0.556; 95% CI=0.394-0.785; P=0.001), and higher educational attainment (OR=0.916; 95% CI=0.884-0.949; P<0.001) were associated with reduced migraine risk. In contrast, predispositions to higher poultry intake (OR=4.690; 95% CI=1.377-15.977; P=0.013) and longer mobile phone use (OR=1.526; 95% CI=1.080-2.157; P=0.017) correlated with increased risk. These associations remained consistent in the multivariable Mendelian randomization analysis after adjusting for stroke and particulate matter air pollution. Our study robustly supports the significant causal roles of specific socioeconomic, behavioral, and dietary factors with physical measurement in the development of migraine. Notably, coffee intake, oily fish intake, and educational attainment appear protective, whereas poultry intake and extensive mobile phone use elevate risk. These insights pave the way for developing targeted preventive strategies for migraine.
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