Causality of blood metabolites and metabolic pathways on Graves' disease and Graves' ophthalmopathy: a two-sample Mendelian randomization study

Abstract

Objectives: There is ample that metabolic dysregulation is involved in Graves' disease (GD) and Graves' ophthalmopathy (GO). Recent studies have identified numerous metabolites associated with GD and GO. However, the causal impact of metabolites on GD and GO remains to be investigated.

Methods: This two-sample Mendelian randomization (MR) analysis investigated the causal relationships between 486 blood metabolites and GD and GO. Sensitivity analysis was also performed to examine heterogeneity and pleiotropy.

Results: MR analysis showed that 9 and 13 metabolites were associated with GD and GO, respectively, each meeting the nominal significance criteria (inverse variance weighted, p < 0.05). Additionally, four metabolic pathways were identified for each condition using network-based MetaboAnalyst 5.0.

Conclusions: The metabolites and pathways discovered in this study could serve as circulating metabolic biomarkers for clinical screening and prevention of GD and GO. They can be also used for further studies on the mechanisms and drug targets in GD and GO.

Keywords: Graves’ disease (GD); Graves’ ophthalmopathy (GO); Mendelian randomization (MR); Metabolites.