Causal associations between chronic hepatitis B and major depressive disorder in East Asian populations: a bidirectional two-sample Mendelian randomization study

BACKGROUND: Epidemiological studies suggest that there is a strong association between chronic hepatitis B (CHB) and major depressive disorder (MDD). However, it remains uncertain whether these associations are causal, as much of the current evidence originates from observational studies that are prone to confounding and reverse causation. METHODS: Single nucleotide polymorphisms robustly associated with CHB were obtained from genome-wide association studies, including 212 453 individuals from the BioBank Japan Project and 4309 individuals of East Asian descent from Korea. Two-sample bidirectional Mendelian randomization analyses were performed to assess the causal association between CHB and MDD using the inverse-variance weighted (IVW), Mendelian randomization-Egger, weighted median, simple mode, and weighted mode methods. RESULTS: Eight single nucleotide polymorphism loci were collectively incorporated as instrumental variables for the CHB-to-MDD analyses. The IVW method showed no evidence of a causal effect of CHB on MDD in the BioBank Japan cohort [odds ratio (OR) = 1.0004, 95% confidence interval (CI): 0.9182-1.0900, P = 0.9921], and Mendelian randomization-Egger analysis yielded a similar null result (OR = 0.9318, 95% CI: 0.6328-1.3723, P = 0.7550). In the reverse direction, the IVW method also showed no evidence of a causal effect of MDD on CHB risk (OR = 0.9836, 95% CI: 0.6766-1.4299, P = 0.9309). CONCLUSION: This study employed Mendelian randomization to find no evidence of a causal relationship between CHB and MDD, challenging prior observational associations.