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

Abstract

Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear. 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. 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. PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.