Association between brain resting-state functional activities and migraine: a bidirectional mendelian randomization study

Abstract Researchers have conducted extensive research on the correlation between brain resting-state functional activities (RSFA) and migraine. However, we still do not fully understand the exact nature of the causal relationship between these RSFA and migraine. We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the causal association between migraine and RSFA. We gathered summary statistics from genome-wide association studies for 191 resting-state functional magnetic resonance imaging phenotypes. We employed various analytical methods for bidirectional two-sample MR analyses. This included inverse variance weighted, weighted median, MR Egger, and the constrained maximum likelihood approaches. We also conducted pleiotropy and heterogeneity analyses to evaluate the robustness and reliability. We found the functional connectivity between the default mode and the central executive network (OR = 1.39, p = 4.77 × 10−4, FDR corrected p value = 0.040) and the intensity of spontaneous brain activity in the calcarine or lingual gyrus within the visual network (OR = 0.74, p = 5.94 × 10−4, FDR corrected p value = 0.040) having a causal effect on the risk of migraine. Our MR analysis provided genetic support for these networks, which may play an important role in influencing migraine susceptibility.