Genetic evidence of the causal relationship between genetically predicted nutrients and psoriatic arthritis

Recently, the importance of nutrients in managing the immune system and inflammation has garnered increasing attention. Research indicates that different nutrients can either reduce or promote inflammation within the immune system. Considering that psoriatic arthritis is a chronic immune-mediated inflammatory disorder, this research sought to investigate potential causal relationships between genetically predicted levels of 25 nutrients and psoriatic arthritis, providing insights into disease pathogenesis and therapeutic strategies.

This study performed a two-sample Mendelian randomization (MR) study along with subsequent meta-analysis. Exposures comprised 25 circulating nutrients, instrumented by genetic variants (IVs), low linkage disequilibrium, and absence of pleiotropy. Outcomes included PsA cases from FinnGen (discovery cohort: N cases/controls = 3537/262,844) and Soomro et al. [23] (validation cohort: N cases/controls = 5065/21,286). Primary causal estimates were derived via inverse-variance weighted (IVW) regression, supplemented by sensitivity analyses (MR-Egger, weighted median, MR-PRESSO) to evaluate heterogeneity, horizontal pleiotropy, and outliers. Fixed-effects meta-analysis integrated estimates across cohorts.

Findings from the meta-analysis revealed a positive association between the risk of psoriatic arthritis and saturated fatty acids (OR = 1.1407, 95% CI 1.0095-1.2890, P = 0.0347) and linoleic acid (OR = 1.1536, 95% CI 1.0321-1.2894, P = 0.0119). No associations were observed for other nutrients. Sensitivity analyses confirmed robustness.

This study provides evidence that genetically predicted higher levels of saturated and linoleic acids are causally associated with increased PsA risk. These findings highlight potential dietary targets for PsA prevention and warrant investigation into lipid-mediated inflammatory pathways in PsA pathogenesis. Key Points • This study demonstrated a significant positive association between genetically predicted circulating levels of saturated fatty acids (OR = 1.141, 95%CI 1.010-1.289)/linoleic acid (OR = 1.154, 95%CI 1.032-1.289) and the risk of psoriatic arthritis. • These findings provided foundational insights for developing dietary interventions aimed at preventing and treating psoriatic arthritis. • Through a two-sample Mendelian randomization coupled with fixed-effects meta-analysis, the robustness of causal inferences was rigorously validated. • Collectively, these results advance the understanding of immunometabolic mechanisms underlying chronic inflammatory disorders.