Role of metabolites in mediating the effect of lipidomes on rheumatoid arthritis

Abstract

Abstract Background Evidence from observational studies and clinical trials suggests that lipidomes are associated with an increased risk of rheumatoid arthritis (RA). However, considering inherent confounding factors and the challenge of reverse causality in observational studies, the direct causal relationship between lipidomes and RA remains unknown. Therefore, we conducted mendelian randomization (MR) as well as mediation analysis to elucidate the causal relationship among lipidomes, RA, and metabolites as a mediator. Methods The bidirectional MR analysis was performed to evaluate the relationship of lipidomes and RA, with a focus on the role of metabolites. Instrumental variables (IVs) were used as the central methodological technique, supplemented by MR-Egger, weighted median, simple mode, as well as weighted mode methods. Results Findings from this study revealed that six lipidomes had a positive correlation with RA, while one showed a negative association. Furthermore, mediation MR analysis results revealed that undecenoylcarnitine (C11:1) served as a mediator for the effect of sterol ester (27:1/20:4) on RA and the mediation effect was calculated to be 7.98%. Conclusions Our study demonstrated the genetic causal effect of lipidomes on RA, emphasizing the potential mediating role of undecenoylcarnitine (C11:1) and providing insights for the clinical intervention of RA.