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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.
CONCLUSIONS: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.
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.
CONCLUSIONS: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.
摘要：
背景：一些研究报道了纯高胆固醇血症（PH）与银屑病之间的关联，但因果关系尚不清楚。
方法：我们使用来自全基因组关联研究的数据，使用双样本双向孟德尔随机化（MR）分析，探索了PH和银屑病之间的因果关系。选择与全基因组显著性水平（p<5×10-8）和低于连锁不平衡水平（r2<0.001）的暴露相关的单核苷酸多态性作为工具变量。随后，我们使用方差逆加权(IVW)，因果推断的MR-Egger和加权中位数(WM)方法。p<0.05被认为是统计学上显著的。使用Cochran的Q检验测试了异质性，使用MR-Egger截距检查水平多效性。进行了留一法分析以评估结果的稳健性和可靠性。
结果：MR结果显示PH对银屑病[IVW：比值比（OR）：1.139，p=0.032；MR-Egger：OR：1.434，p=0.035；WM：OR：1.170，p=0.045]和银屑病关节炎（PsA）（IVW：OR：1.210，p=0.049；MR-Egger回归：0.033，p：0.028然而,PH与寻常型银屑病以及其他未指明的银屑病之间没有因果关系。反向MR结果表明PsA和PH之间存在负因果关系（IVW：OR：0.950，p=0.037）。不存在异质性和水平多效性，这些结果被证实是稳健的。
结论：PH对银屑病和PsA有积极的副作用，和PsA可以降低患PH的风险。
方法：我们使用来自全基因组关联研究的数据，使用双样本双向孟德尔随机化（MR）分析，探索了PH和银屑病之间的因果关系。选择与全基因组显著性水平（p<5×10-8）和低于连锁不平衡水平（r2<0.001）的暴露相关的单核苷酸多态性作为工具变量。随后，我们使用方差逆加权(IVW)，因果推断的MR-Egger和加权中位数(WM)方法。p<0.05被认为是统计学上显著的。使用Cochran的Q检验测试了异质性，使用MR-Egger截距检查水平多效性。进行了留一法分析以评估结果的稳健性和可靠性。
结果：MR结果显示PH对银屑病[IVW：比值比（OR）：1.139，p=0.032；MR-Egger：OR：1.434，p=0.035；WM：OR：1.170，p=0.045]和银屑病关节炎（PsA）（IVW：OR：1.210，p=0.049；MR-Egger回归：0.033，p：0.028然而,PH与寻常型银屑病以及其他未指明的银屑病之间没有因果关系。反向MR结果表明PsA和PH之间存在负因果关系（IVW：OR：0.950，p=0.037）。不存在异质性和水平多效性，这些结果被证实是稳健的。
结论：PH对银屑病和PsA有积极的副作用，和PsA可以降低患PH的风险。
