Objective To investigate the associations of circulating inflammatory proteins and risk of psoriasis by using a two-sample Mendelian randomization (MR) approach. Methods Based on the genome-wide association study (GWAS) of inflammatory proteins and psoriasis, genetic variants associated with circulating inflammatory proteins were selected as instrumental variables (IVs), and genetic association data of psoriasis were extracted. The inverse-variance weighted method was used as the primary MR method, with statistical power analysis conducted to evaluate the test power. MR-Egger regression, weighted median, maximum likelihood, and MR Pleiotropy RESidual Sum and Outlier (PRESSO) tests were used to evaluate the influence of horizontal pleiotropy on the MR association estimates. Additionally, as sensitivity analysis, a GWAS of psoriasis from the FinnGen database was used as a replication dataset to evaluate the robustness of the results. Results A total of 558 single nucleotide polymorphisms associated with 74 inflammatory proteins were included. After False Discovery Rate (FDR) corrections, genetically predicted circulating levels of C-X-C motif chemokine ligand 9 (CXCL9) [odds ratio (OR)=1.76, 95% confidence interval (CI) (1.46, 2.11), P=2.31×10?9], C-C motif chemokine ligand 19 (CCL19) [OR=1.41, 95%CI (1.22, 1.62), P=2.97×10?6], and tumor necrosis factor-beta (TNFB) [OR=1.31, 95%CI (1.13, 1.52), P=3.56×10?4] were found to be significantly associated with an increased risk of psoriasis. Sensitivity analyses yielded similar results. Statistical power analysis indicated that the power to detect these associations was greater than 99%. Conclusion Genetically predicted circulating CXCL9, CCL19, and TNFB levels are positively associated with risk of psoriasis.
