Moreover, this study systematically bridges epidemiological causality (MR-derived OR = 2.04, p = 0.011) with molecular convergence through four synergistic analytical layers: (1) 230 co-dysregulated genes at the COPD–insomnia interface, demonstrating immune–inflammatory axis dominance; (2) TNFAIP3 as a redox rheostat bridging NF-κB signaling and circadian rhythm pathways; (3) TNFAIP3, CXCR4, and PTGS2 as triple diagnostic signatures; and 4) TNFAIP3-targeting agents with dual anti-inflammatory and neuroregulatory abilities [28]. Here, NFKB1 is linked to insomnia measurement.