The Casual Associations Between Brain Functional Networks and Fibromyalgia: A Large-Scale Genetic Correlation and Mendelian Randomization Study.

While the central mechanisms of fibromyalgia have gained attention, the causal effects between brain networks and fibromyalgia remain unclear. Two-sample Mendelian randomization and Linkage Disequilibrium Score Regression were performed to investigate the relationship between 191 rsfMRI traits and 8 fibromyalgia-related traits. A total of 4 rsfMRI traits were genetically correlated with trouble falling asleep, 11 with back pain for 3+ months, 16 with pain all over the body, 14 with insomnia, 5 with fibromyalgia, 4 with fibromyalgia, and 3 with malaise and fatigue. Pheno801 has significant causal effects on malaise and fatigue (OR = 1.0022, p = 0.01), fibromyalgia (finngen) (OR = 1.5055, p = 0.03), and insomnia (OR = 1.4063, p = 0.04). Pheno1696 significantly impacts fibromyalgia-related comorbidities (OR = 1.002, p = 0.02), trouble falling asleep (OR = 1.0285, p = 0.04), malaise and fatigue (OR = 1.0011, p = 0.04), and pain all over the body (OR = 0.9967, p = 0.04). Pheno103 has marked effects on fibromyalgia (finngen) (OR = 0.7477, p = 0.02), malaise and fatigue (OR = 0.9987, p = 0.03), and pain all over the body (OR = 1.0033, p = 0.03). Our findings suggest that targeting these networks could effectively prevent or alleviate fibromyalgia.