Association between Chronic Hepatitis B and Osteoporosis: a two-sample mendelian randomization study

Introduction: Evidence suggests that metabolic abnormalities caused by chronic hepatitis B (CHB) are associated with osteoporosis (OP). However, whether there are causal relationships between CHB and OP remains undetermined. The present study assessed the causal effect of CHB on OP via two-sample Mendelian randomization (MR). Methodology: We performed a two-sample MR study using summary-level data from genome-wide association studies (GWASs) of the CHB and OP patients derived from the BioBank Japan Project (BBJ). The single-nucleotide polymorphisms (SNPs) associated with CHB were selected as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary statistical method to identify the consequence between CHB and OP. We additionally applied the other methods (weighted median method, simple mode method, and weighted mode method) to examine the consistency of the results. Cohran`s Q test and Pleiotropy test were used to determine the horizontal pleiotropy and heterogeneities of these IVs on OP. The leave-one-out sensitivity test was used to evaluate the effect of a single IV on the ME results. Results: Inverse‐variance weighted analyses suggested that CHB was significantly associated with OP (OR = 1.011, 95% CI = 1.011 - 1.063, p = 0.005) without pleiotropy. The results of the heterogeneity test and the pleiotropy test revealed free heterogeneity and no pleiotropy in our IVW analysis (p > 0.05). Similar associations were detected with the weighted median and weighted mode methods (OR = 1.042, 95% CI = 1.007-1.079, p = 0.017; OR = 1.011, 95% CI = 1.011-1.063, p = 0.032). Conclusions: This MR study revealed the causal effect of chronic hepatitis B on osteoporosis in East Asians.