Exploring causal links between brain functional networks and neurodegenerative disease risk using Mendelian randomization.

Connectivity between the SN, DMN, and CEN shows a marked reduction (b = −0.0512, se = 0.0133, p = 0.00011), with this decrease being highly significant (95% CI: −0.0772 to −0.0252) and OR = 0.9501, indicating a 4.99% reduction in connectivity (95% CI: 0.9257–0.9751), remaining significant after multiple comparisons and FDR adjustment (p_fdr = 0.0212).

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For instance, in the case of PD, even though there may not be significant structural differences between PD patients and a control group, there are notable variations in functional network connectivity.

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These results highlight methodological challenges in detecting weak causal effects (e.g., OR≈1 for AD) and underscore the robustness of high-powered associations (ALS/MS/PD), emphasizing the necessity of integrating power assessments when interpreting MR outcomes, particularly for borderline significant findings or studies with constrained sample sizes.

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