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Eurasian Journal of
Medicine and Oncology Helicobacter pylori infection and Alzheimer’s disease

we also used four more useful techniques: MR-Egger, Anti-H. pylori UREA was found to raise AD risk (odds
weighted median, weighted mode, and simple mode. SNPs ratio [OR] = 1.071; 95% confidence interval (CI) = 1.004 –
with genome-wide significance (p<5 × 10 ) were selected 1.143; p=0.038) (Figure 1).
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as IVs for both anti H. pylori antibodies and AD. The Anti-H. pylori UREA and AD were found to be similarly
F-statistic for each SNP was calculated to assess the strength associated in the two-sample MR analysis, with an OR of
of the selected instruments. SNPs with an F-statistic <10 1.076 (95% CI = 1.010 – 1.147; p=0.024) (Figure 2). Detailed
were excluded to avoid bias from weak instruments. The information on F-values as well as LD independent SNPs
LD threshold was established at r² < 0.001, with a genetic related to exposure (H. pylori antibodies) can be found in
distance of 10,000 kb, to guarantee SNP independence. We Tables S1-S6 (available in Supplementary File).
computed the F-statistic for the selected SNPs, applying
a threshold of >10 to evaluate the strength of the IVs. To 3.2. Reverse MR analysis
evaluate pleiotropy and heterogeneity, we used Cochran’s In the reverse MR study exploring the correlation among
Q statistic as well as the MR-Egger test, respectively. H. pylori and AD, both the two-sample MR and GSMR
2.3. GSMR analysis analyses failed to identify a meaningful correlation among
the two. These results indicate that AD does not appear
GSMR is an advanced analytical method that integrates to influence H. pylori infection risk. Further details are
genome-wide summary data from multiple independent presented in Tables S7 and S8 (Supplementary File).
studies, flexibly utilizing several relatively independent IVs
for MR analysis. This approach aims to analyze the causal 3.3. Sensitivity analysis
links among various illnesses and exposure determinants, The assessment of H. pylori infection’s effect on AD
providing more reliable inference results. For the genetic revealed no substantial heterogeneity, as per the Cochran’s
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instruments associated with anti-H. pylori antibodies, we Q test. The MR-Egger intercept test also found no proof
employed a clumping algorithm to identify SNPs that are of horizontal pleiotropy. Scatter plots demonstrated the
genome-wide significant for each trait, applying an LD impact of the infection on AD across five MR approaches,
threshold of r² = 0.001 and a significance threshold of with a positive slope indicating a direct correlation
p<5 × 10 . The reference for LD estimation was derived (Figure S1 in Supplementary File). Furthermore, as
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from the 1000 Genomes Project (1000G) phase 3 European indicated by leave-one-out analysis, specific SNPs are
samples. In the reverse analysis, we selected independent unlikely to significantly influence the causal estimates
SNPs from the GWAS summary statistics for AD by (Figure S2 in Supplementary File). Together, these findings
establishing a LD threshold of r² < 0.001 and a significance strengthen the robustness of the observed associations.
threshold of p<5 × 10 . We established a HEIDI outlier
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threshold of 0.01 to exclude instruments with significant 4. Discussion
putative pleiotropic effects. This study explored the causal link of H. pylori infection

2.4. Sensitivity analyses with AD. Employing MR techniques, a substantial positive
association was found between AD and anti-H. pylori
We carried out a comprehensive set of sensitivity tests to UREA antibodies, with an OR of 1.071 (95% CI = 1.004
confirm the causal impact of H. pylori infection on AD. – 1.143, p=0.038). This result highlights that higher levels
Cochran’s Q statistic was applied to analyze any possible of these antibodies may correlate with a higher chance of
heterogeneity in the data. Horizontal pleiotropy was AD development, thereby offering new insights for clinical
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analyzed by employing the MR-Egger intercept analysis. and public health interventions. Importantly, the notable
Furthermore, by systematically excluding each SNP, a association with anti-H. pylori UREA underscores its
leave-one-out investigation was carried out to see whether distinct function in AD pathogenesis, which may inform
any single SNP had a considerable influence on the results. future therapeutic and preventive approaches to mitigate
RStudio and R (version 4.2.0) were used for all analyses, the impact of this neurodegenerative disorder.
including the R packages gsmr, TwoSampleMR, and
MR-PRESSO. The strong correlation between the two suggests
that H. pylori infection is critical in the etiology of AD.
3. Results Investigations indicated that H. pylori can induce chronic
inflammation and immune responses, potentially resulting
3.1. Causal effect of H. pylori infection on AD
in neural damage. Moreover, the infection may release
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In our initial investigation, we utilized GSMR to examine neurotoxic substances that impair neuronal function and
the correlation among AD and six anti-H. pylori antibodies. survival, thereby accelerating cognitive decline. Although
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Volume 9 Issue 3 (2025) 289 doi: 10.36922/EJMO025140087