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Background: Accumulating evidence suggests an intimate relationship between residual cholesterol and psoriatic arthritis (PsA). However, owing to confounding and reverse causality, this relationship remains unclear in observational studies. The aim of our study was to identify the causal relationship of residual cholesterol with PsA by Mendelian randomization.
Methods: In this study, we obtained genetic variants linked with residual cholesterol levels in the largest genome-wide association study (GWAS) on Europeans. We also selected genetic variants corresponding effect estimates on PsA risk from a large GWAS. To make the results more stable, we used six robust analytical methods for the MR analysis. The results of MR analyses in the discovery/validation set were combined using the fixed-effect model. Furthermore, we also used MR Steiger to assess the possible direction of causal estimate between them.
Results: In the discovery set, gene prediction found that for every 1 SD increase in residual cholesterol levels, the relative risk of PsA increased 1.177 (95% CI: 1.024 - 1.353). In the validation set, we observed that for every 1 SD increase in residual cholesterol levels, the relative risk of PsA increased 1.185 (95% CI: 1.068 - 1.316). In the meta-analysis, we found residual cholesterol levels could increase the risk of PsO. In addition, MR Steiger also found reverse causality between them.
Conclusions: This study supports evidence of a relationship of residual cholesterol with PsA.
DOI: 10.7754/Clin.Lab.2025.250118
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