Multivariate Mendelian randomization study on the relationship between smoking,alcohol consumption and migraine
Objective To explore the causal relationship between smoking,alcohol consumption and migraine.Methods A two-sample multivariate Mendelian randomized(MR)study was conducted with single nucleotide polymorphism(SNP)as instrumental variable,smoking and alcohol consumption as exposure factors and migraine as outcome.Inverse variance weighting(IVW)method,weighted median method,MR-Egger regression method,weighted model method,and simple model method were used to evaluate the effects of smoking and alcohol consumption on migraine;at the same time,reverse MR analysis was performed to explore reverse causality.Cochran's Q test was used for heterogeneity analysis,MR-Egger intercept method was used to analyze pleiotropy,and remain-one method was used to test whether there was bias caused by a specific SNP,and funnel plot was used to evaluate the reliability of causal association.Results Forward analysis showed that the OR value of IVW method was 1.39(95％CI:1.06-1.83),the difference was statistically significant(P＜0.05),and the OR value of weighted median method was the same as its direction;after adjusting for the influence of alcohol consumption in multivariate analysis,the OR value of IVW method was 1.71(95％CI:1.53-1.89),and the difference was statistically significant(P＜0.05).Reverse analysis showed no causal link between migraines and smoking.Forward analysis showed that the OR value of IVW method was 0.58(95％CI:0.43-0.78),and the difference was statistically significant(P＜0.05),the OR value of weighted median method and weighted model method was the same as its direction;after adjusting the influence of smoking in multivariate analysis,the OR value of IVW method was 0.66(95％CI:0.40-0.92),and the difference was statistically significant(P＜0.05),and the direction of OR value of multivariate MR-Egger regression method was the same as that of IVW method.Reverse analysis showed that the OR value of IVW method was 0.94(95％CI:0.91-0.96),and the difference was statistically significant(P＜0.05).The forward analysis showed that there was heterogeneity between smoking,alcohol consumption and migraine,but no pleiotropy;the reverse analysis showed that there was heterogeneity and no pleiotropy between migraine and smoking.The leave-one method showed that no single SNP had a significant impact on the results,and the funnel plot showed that the instrumental variables were distributed symmetrically,and the results were unbiased and relatively stable.Conclusion This study provides genetic evidence supporting that smoking is a risk factor for migraine,while the relationship between alcohol consumption and reduced migraine risk may be partially due to reverse causality.
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