Causal Relationship Between Helicobacter pylori OMP Antibodies and Iron-Deficiency Anemia: A Mendelian Randomization
Yuxin Ge1, Xiaopan Lv1, Dongxiao Hao1
1School of Clinical Medicine, Shandong Second Medical University.
Abstract:
Previous observational studies have suggested a potential causal relationship between Helicobacter pylori (H. pylori) infection and iron-deficiency anemia (IDA). However, the evidence for causal inference remains contentious, as observational studies are prone to confounding factors that may bias the results. Additionally, the mechanisms underlying the association between H. pylori infection and IDA remain incompletely elucidated. To address these gaps and delve deeper into the nature of the relationship between H. pylori and IDA, this study conducted a bidirectional two-sample Mendelian randomization (MR) analysis, which is less susceptible to confounding and reverse causality compared to traditional observational designs. Inverse-variance weighted (IVW) was used as the primary analytical method, with weighted median, MR-Egger regression, weighted mode, and simple mode as supplementary approaches. Seven common serum H. pylori antibodies were selected as exposure factors for the forward MR analysis. A series of sensitivity analyses was conducted to assess the reliability of the main MR assumptions and ensure the robustness of the study results. Reverse MR analysis was further performed to assess the potential reverse causality, and the results confirmed that there is no reverse causal relationship between IDA and H. pylori infection. Genetically predicted serum levels of H. pylori outer membrane protein (OMP) antibodies were positively associated with an increased risk of IDA (odds ratio [OR] = 1.077, 95% CI 1.010-1.148, P = 0.02194), while no causal association was observed for other antibodies. Reverse MR excluded reverse causality between IDA and H. pylori infection. This study first performed antibody-stratified two-sample MR analysis for seven H. pylori antibodies, suggesting that elevated OMP antibody levels increase IDA susceptibility and providing reliable causal evidence to enrich relevant research.
Insights
Helicobacter pylori (H. pylori) infection may cause iron-deficiency anemia (IDA). This study found that H. pylori outer membrane protein antibodies increase IDA risk, confirming a causal link. Further research is needed to understand the mechanisms involved.
Area of Science:
- Genetics and Epidemiology
- Gastroenterology
- Hematology
Background:
- Observational studies suggest a link between Helicobacter pylori (H. pylori) infection and iron-deficiency anemia (IDA).
- Confounding factors and potential reverse causality limit traditional observational study findings.
- Mechanisms connecting H. pylori and IDA require further elucidation.
Purpose of the Study:
- To investigate the causal relationship between H. pylori infection and IDA using a robust Mendelian randomization approach.
- To identify specific H. pylori antibodies associated with IDA risk.
- To assess potential reverse causality between IDA and H. pylori infection.
Main Methods:
- Bidirectional two-sample Mendelian randomization (MR) analysis was employed.
- Inverse-variance weighted (IVW) was the primary method, supported by weighted median and MR-Egger regression.
- Seven common serum H. pylori antibodies were analyzed as exposure factors; sensitivity and reverse MR analyses were performed.
Main Results:
- Genetically predicted serum levels of H. pylori outer membrane protein (OMP) antibodies showed a positive association with increased IDA risk (OR = 1.077, P = 0.02194).
- No significant causal association was found for other H. pylori antibodies.
- Reverse MR analysis confirmed no reverse causality between IDA and H. pylori infection.
Conclusions:
- Elevated H. pylori OMP antibody levels causally increase susceptibility to iron-deficiency anemia.
- This study provides reliable genetic evidence for a causal link between specific H. pylori antibodies and IDA.
- Findings contribute to understanding the pathogenesis of IDA in the context of H. pylori infection.
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