No evidence for a causal link between Helicobacter pylori infection and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study

Abstract

Although clinical studies have shown the possible relationship between <i>Helicobacter pylori</i> (<i>H. pylori</i>) infection and the development of nonalcoholic fatty liver disease (NAFLD), their causal relationship is still unknown. This bidirectional Mendelian randomization (MR) study aimed to investigate the causal link between <i>H. pylor</i>i infection and NAFLD. Two previously reported genetic variants SNPs rs10004195 and rs368433 were used as the instrumental variables (IVs) of <i>H. pylori</i> infection. The genetic variants of NAFLD were extracted from the largest genome-wide association study (GWAS) summary data with 1,483 cases and 17,781 controls. The exposure and outcome data were obtained from the publicly available GWAS dataset. Then, a bidirectional MR was carried out to evaluate the causal relationship between <i>H. pylori</i> infection and NAFLD. In addition, the GWAS data were also collected to explore the causal relationship between <i>H. pylori</i> infection and relevant clinical traits of NAFLD, including triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and body mass index (BMI). Genetically predicted <i>H. pylori</i> infection showed no association with NAFLD both in FinnGen GWAS (OR, 1.048; 95% CI, 0.778-1.411; value of <i>p</i> = 0.759) and the GWAS conducted by Anstee (OR, 0.775; 95% CI, 0.475-1.265; value of <i>p</i> = 0.308). An inverse MR showed no causal effect of NAFLD on <i>H</i>. <i>pylori</i> infection (OR,0.978;95% CI, 0.909-1.052; value of <i>p</i> = 0.543). No significant associations were observed between <i>H</i>. <i>pylori</i> infection and the levels of triglycerides, LDL-C, HDL-C, or FBG, while <i>H. pylori</i> infection was associated with an increase in BMI. These results indicated that there was no genetic evidence for a causal link between <i>H. pylori</i> and NAFLD, suggesting that the eradication or prevention of <i>H. pylori</i> infection might not benefit NAFLD and vice versa.