METHODS: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran\'s Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings.
RESULTS: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%.
CONCLUSIONS: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.
方法:我们利用公开的全基因组关联研究数据进行双向双样本,孟德尔随机两步研究。采用逆方差加权法作为主要分析技术。MR-Egger和加权中位数作为补充分析方法。MR-PRESSO,Cochran的Q测试,和MR-Egger截距检验用于敏感性分析,以确保我们研究结果的稳健性。
结果:孟德尔随机分析显示磷脂酰胆碱(PC)水平(18:1_20:4)(OR:0.950,95%CI:0.929-0.972,p=6.65×10-6),磷脂酰乙醇胺(O-18:1_20:4)(OR:0.938,95%CI:0.906-0.971,p=2.79×10-4),三酰甘油(TAG)(56:6)(OR:0.937,95%CI:0.906-0.969,p=1.48×10-4)和TAG(56:8)(OR:0.918,95%CI:0.876-0.961,p=2.72×10-4)与特应性皮炎的风险呈负相关。相反,PC(18:1_20:2)(OR:1.053,95%CI:1.028~1.079,p=2.11×10-5)和PC(O-18:1_20:3)(OR:1.086,95%CI:1.039~1.135,p=2.47×10-4)与特应性皮炎风险呈正相关。反向孟德尔随机分析的结果表明,特应性皮炎对179种血浆脂质没有明显的因果关系。循环IL-18R1的水平被确定为与较高水平的PC(18:1_20:2)相关的特应性皮炎风险增加的介质,占调解比例9.07%。
结论:我们的研究表明,血脂可以影响循环炎症蛋白,可能是特应性皮炎的致病因素之一。靶向血浆脂质水平作为特应性皮炎的治疗提出了一种潜在的新方法。