3.6 Causal Effects of EBV on CLA
For EBV, we explored the relationship between eight EBV-related antibodies and CLA. The MR-Egger analysis indicated a potential reduction in the risk of CLA for the EBV EA-D antibody levels (OR = 0.145, 95% CI = 0.038–0.551, p = 0.016). However, IVW and weighted median analyses did not find significant associations for any of the eight antibodies, with p-values exceeding 0.05(Figure. 2).
For the eight EBV-related antibodies, no unbalanced horizontal pleiotropy was found in any of the instruments (p > 0.05). Two antibodies (EBV VCA p18 antibody levels and Anti-EBV EA IgG levels) showed heterogeneity (p = 0.043; p = 0.031), while there was no evidence of heterogeneity among the remaining six antibodies (Figure. 3h-o).
Furthermore, all funnel plots indicated a slight presence of pleiotropy, suggesting a potential single instrumental variable affecting the estimated causal effect (Figure. 4). The leave-one-out analysis showed that no single SNP strongly influenced the overall effect of exposure on the outcome (Figure. 5).
In summary, our results suggest a causal relationship between HHV-6 and CLA, while no such relationships were observed for other herpes viruses. Sensitivity analyses and tests for pleiotropy and heterogeneity support the robustness of these findings.