<i>Helicobacter pylori</i> Infection and Iron Deficiency Anemia: A Mendelian Randomization Study

Background: This study is to investigate the causal relationship between Helicobacter pylori infection and iron deficiency anemia (IDA) using a two-sample Mendelian randomization (MR) approach. Methods: A two-sample MR analysis was conducted using eleven single-nucleotide polymorphisms (SNPs) associated with H. pylori infection from genome-wide association studies (GWAS) data. Outcome datasets included IDA, hemoglobin (HGB) levels, and iron metabolism-related indices [ferritin, transferrin saturation (TSAT), serum iron, and total iron-binding capacity (TIBC)]. The primary analysis used the inverse-variance weighted (IVW) method, with validation via the MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method. Results: Helicobacter pylori infection significantly reduced the risk of IDA (IVW: OR = 0.9986, 95% CI = 0.9977 - 0.9994, P = 9.8e-5; MR-PRESSO: OR = 0.9986, 95% CI = 0.9980 - 0.9991, P = 0.0064). No significant effect was observed on HGB levels or other iron metabolism-related indices. Conclusions: This study provides genetic evidence that H. pylori infection is not a causative factor for IDA and may confer a protective effect. If validated, these findings could influence the management of H. pylori infection and IDA prevention strategies, particularly in populations without severe gastrointestinal pathologies.