Systematic Review of Mendelian Randomization Studies on Helicobacter pylori-Associated Health Outcomes

Helicobacter pylori (HP) infection has been linked to nearly 90 different health conditions, including gastric malignant and premalignant lesions. Recently, Mendelian randomization (MR) has gained popularity to overcome limitations in observational studies. This review aims to compile MR studies on the causal relationship between HP infection and health outcomes, systematically assess the quality of individual studies, evaluate the overall evidence in comparison with other existing data, and identify common strengths and weaknesses in order to guide future research directions on HP-associated health outcomes.

Eligible studies were identified from the two major biomedical literature databases, PubMed and Embase. After removing overlaps, we found 33 unique records published by July 10, 2024. Among those, 16 were qualified for full-text review as original research papers presenting MR analysis with HP infection as the primary exposure of interest.

Among the 16 studies, one was one-sample MR study and the rest 2-sample MR studies. All except one were conducted on individuals of European descent. Health outcomes studied include four metabolic conditions, four cardiovascular diseases (CVDs), five gastrointestinal conditions, and three other miscellaneous conditions. All used genome-wide association study (GWAS) data on HP serology to select instrumental variants, ranging from 1 to 84. Nine out of 16 studies concluded that HP had a causal association with the disease of their interest. However, not all papers fully examined whether MR key assumptions were met and there are inaccurate descriptions and misinterpretations in many papers. In addition, there are inconsistencies between studies, depending on the choice of exposure GWAS from which instrumental variants were chosen.

Overall, published MR studies concerning HP infection and various health outcomes to date are limited in their quality/integrity. The results from HP eradication trials completed or in progress may help address the causality of some of the health outcomes with high incidence rates. In addition, MR studies in non-European populations with higher HP prevalence are warranted.