Role of miRNAs in the pathogenesis of psoriasis and psoriatic arthritis: a genome-wide Mendelian randomization study.

Abstract

Background: MicroRNAs (miRNAs) are critical in the onset and treatment of skin diseases, but the miRNAs causally associated with psoriasis (PSO) and psoriatic arthritis (PsA) remain unclear. This study aims to identify miRNAs with causal associations with PSO and PsA.

Methods: Five Mendelian randomization (MR) methods were employed, using miRNA expression quantitative trait loci (mirQTL) data as exposure variables and PSO and PsA as outcome variables. This approach was used to uncover the causal links of miRNAs with both PSO and PsA, with robust sensitivity analyses ensuring the stability of our findings. Finally, miRNet and enrichment analyses were used to predict target genes of the causal miRNAs and their potential biological roles.

Results: Our robust findings indicated that miR-27b-3p, miR-204-5p, and miR-6891-3p were notably associated with an enhanced risk of PSO. Additionally, miR-6891-3p was greatly associated with an enhanced risk of PsA. Conversely, miR-29c-3p, miR-181a-3p, miR-181a-5p, miR-181b-5p, and miR-199a-3p were substantially associated with a reduced risk of both PSO and PsA. Enrichment analyses revealed that the target genes of these causal miRNAs were markedly enriched in biological pathways such as apoptosis, Wnt, and PI3K-AKT signaling.

Conclusion: This study identifies eight miRNAs causally associated with PSO and five miRNAs associated with PsA, with no observed heterogeneity or pleiotropy. These findings offer potential biomarkers for the diagnosis and treatment of PSO and PsA. Key Points • We conducted the first genome-wide MR study to explore the causal relationships between miRNAs and PSO and PsA. • The study found stable and reliable causal effects of 8 miRNAs on PSO and 5 miRNAs on PsA. • These miRNAs provide important insights into elucidating the pathophysiological mechanisms of PSO and PsA and developing new therapeutic approaches.