Genetically predicted modifiable risk factors for Helicobacter pylori infection: A Mendelian randomization study.

This Mendelian randomization (MR) study aimed to investigate causal relationships between modifiable factors and Helicobacter pylori (H pylori) infection risk. These factors included lifestyle, socioeconomic, and nutritional variables. Bidirectional 2-sample MR analyses were conducted using genetic instruments derived from genome-wide association studies in Europeans. Primary analyses employed inverse variance weighting, supported by MR-Egger, weighted median, and pleiotropy-robust methods. Sensitivity analyses included Cochran Q test, MR-Egger intercept, and leave-one-out validation. Potential reverse causation was evaluated by reverse MR. Genetically predicted smoking initiation (odds ratio [OR]: 1.079, 95% confidence interval [CI]: 1.013-1.148, P = .017), prolonged television viewing (OR: 1.233, 95% CI: 1.090-1.395, P = .001), insomnia (OR: 3.691, 95% CI: 1.119-12.180, P = .032), tea consumption (OR: 2.122, 95% CI: 1.087-4.142, P = .027), and elevated body mass index (OR: 1.052, 95% CI: 1.007-1.099, P = .024) exhibited significant causal associations with increased infection risk. Conversely, genetically instrumented higher educational attainment (OR: 0.769, 95% CI: 0.663-0.891, P < .001), cereal intake (OR: 0.803, 95% CI: 0.669-0.963, P = .018), vitamin D sufficiency (OR: 0.796, 95% CI: 0.649-0.976, P = .028), moderate-to-vigorous physical activity (OR: 0.339, 95% CI: 0.144-0.796, P = .013), alcohol consumption (OR: 0.140, 95% CI: 0.034-0.579, P = .007), ferritin levels (OR: 0.624, 95% CI: 0.399-0.975, P = .038), and transferrin saturation (OR: 0.803, 95% CI: 0.670-0.962, P = .017) demonstrated protective effects. An increased level of transferrin was associated with higher risk (OR: 1.139, 95% CI: 1.012-1.282, P = .031). Sensitivity analyses confirmed robustness, with no evidence of horizontal pleiotropy (MR-Egger intercept P > .05) or outlier-driven effects. Reverse MR revealed no significant influence of H pylori infection on exposure traits (P > .05). These findings suggest several modifiable factors contribute to H pylori infection risk. This study provides genetic evidence that multiple modifiable factors are causally associated with H pylori infection risk. Our findings highlight the potential of integrated public health strategies, promoting smoking cessation, physical activity, dietary optimization, weight control, and socioeconomic development, as effective measures for primary prevention.