Causal Relationship Between Mitochondrial Characteristics and Inflammatory Bowel Disease and Its Subtypes: Evidence for Mendelian Randomization

Abstract

Objective

The research was designed to explore the causal relationship between the changing landscape of 63 mitochondrial proteins and inflammatory bowel disease (IBD) by Mendelian randomization.

Methods

Use SNPs significantly associated with IBD and their subtypes as instrumental variables. Various methods were utilized to assess the causal relation between mitochondrial function and the onset of IBD and their subtypes.

Results

The results after FDR on p values indicated that Peptide chain release factor 1-like was a causative factor for IBD. NADH dehydrogenase [ubiquinone] flavoprotein 2, hydroxymethylglutaryl-CoA synthase 9, pyruvate carboxylase, apoptosis-inducing factor 1, and transmembrane protein 70 with inflammatory bowel disease were identified as protective factors. Peptide chain release factor 1-like and NADH dehydrogenase [ubiquinone] flavoprotein 2 were identified as causal and protective factors for IBD, respectively. In addition, GrpE protein homolog 1, 39S ribosomal protein L33, and tRNA pseudouridine synthase A are pathogenic in Crohn's disease, and Hydroxymethylglutaryl-CoA synthase and Pyruvate carboxylase are protective factors. The MR-presso method rejected outlier SNPs. The relative stability of the outcome data was assessed and validated at multiple levels by various statistical tests including pleiotropy test, heterogeneity test, and Steiger test.

Conclusion

This study established a causal relationship between mitochondrial biological function and IBD, including its subtypes.