To explore the potential causal relationship between Crohn’s disease (CD) and nonalcoholic fatty liver disease (NAFLD) based on two-sample Mendelian randomization (MR) method.

The datasets of CD and NAFLD were obtained from IEU Open GWAS database. The causality between CD and NAFLD was analyzed by using five methods: inverse variance weighted (IVW) method, MR-Egger regression, weighted median estimator (WME), simple mode and weighted mode. The stability and reliability of the research results were evaluated by Cochran’s Q test, MR-Egger regression, MR-PRESSO, Leave-one-out, funnel diagram and forest plot.

The causal effects obtained by these five methods were in the same direction. IVW analysis showed that there was causal relationship between CD and NAFLD (OR=1.034, 95%CI: 1.007-1.061, P=0.013). Heterogeneity analysis revealed no significant heterogeneity between IVW test (Q=29.041, P=0.969) and MR-Egger test (Q=29.021, P=0.960). No outlier single nucleotide polymorphisms (SNPs) were detected by MR-PRESSO analysis, and horizontal pleiotropy was excluded (P=0.888). MR-Egger regression analysis (P=0.209) also detected no evidence of horizontal pleiotropy. Leave-one-out analysis showed that no single SNPs significantly affected the overall effect.

From the perspective of heredity, this study preliminarily reveals that CD may have causal relationship with the increase of NAFLD risk. Positive correlation between CD and NAFLD is a risk factor for increasing the risk of NAFLD.