The causal relationship between pure hypercholesterolemia and psoriasis: A bidirectional, two-sample Mendelian randomization study.

ABSTRACT

BACKGROUND: Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear. METHODS: We explored the causal effect between PH and psoriasis using two-sample bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies. Single nucleotide polymorphisms related with exposures at the genome-wide significance level (p < 5×10-8 ) and less than the linkage disequilibrium level (r2  < 0.001) were chosen as instrumental variables. Subsequently, we used inverse variance weighting (IVW), MR-Egger and weighted median (WM) methods for causal inference. p < 0.05 was considered statistically significant. Heterogeneity was tested using Cochran's Q-test, and horizontal pleiotropy was examined using the MR-Egger intercept. Leave-one-out analyses were performed to assess the robustness and reliability of the results. RESULTS: MR results showed a positive causal effect of PH on psoriasis [IVW odds ratios (OR) 1.139, p = 0.032; MR-Egger OR 1.434, p = 0.035; WM OR 1.170, p = 0.045] and psoriatic arthritis (PsA) (IVW OR 1.210, p = 0.049; MR-Egger regression OR 1.796, p = 0.033; WM OR 1.317, p = 0.028). However, there is no causal relationship between PH and psoriasis vulgaris as well as other unspecified psoriasis. Inverse MR results suggested a negative causal relationship between PsA and PH (IVW OR 0.950, p = 0.037). No heterogeneity and horizontal pleiotropy exist, and these results were confirmed to be robust. CONCLUSION: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.