Table_3_Causality of unsaturated fatty acids and psoriasis a Mendelian randomization study.DOCX

BackgroundMany observational studies have identified a link between unsaturated fatty acids and psoriasis. However, they contain reverse causality and confounding factors, and there is no definite causal study between unsaturated fatty acids and psoriasis.
ObjectivesAnalysis of causality between unsaturated fatty acids and psoriasis by Mendelian randomization.
MethodsWe used IEU Open GWAS Project, omega-3 PUFA and omega-6 PUFA data from 114,999 subjects, MUFA data from 13,535 subjects, and psoriasis data from 4,510 cases and 212,242 controls were included. We employed the inverse-variance weighted (IVW) method as the primary analytical approach and four additional MR methods. Moreover, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane’s Q and MR-Egger intercept tests, respectively. Finally, we performed sensitivity analyses to enhance our findings’ precision and veracity.
ResultsIVW results showed no causal effect of omega-3 PUFA on psoriasis (p = 0.334; OR, 0.909; 95% CI, 0.748–1.104), omega-6 PUFA cause psoriasis (p = 0.046; OR, 1.174; 95% CI, 1.003–1.374), MUFA cause psoriasis (p = 0.032; OR, 1.218; 95% CI, 1.018–1.457), no causal effect of omega-3 PUFA in psoriasis (p = 0.695; OR, 0.989; 95% CI, 0.937–1.044), no causal effect of omega-6 PUFA in psoriasis (p = 0.643; OR, 1.013; 95% CI, 0.960–1.068), psoriasis is not causal to MUFA (p = 0.986; OR, 1.000; 95% CI, 0.949–1.055). Heterogeneity, horizontal pleiotropy, and sensitivity analyses showed reliable results.
ConclusionWe found that circulating omega-6 PUFA and MUFA cause psoriasis, while omega-3 PUFA do not. Treatments that lower circulating omega-6 PUFA and MUFA are effective in psoriasis. After a better understanding of fatty acid intake and circulation, the population can be advised to regulate their diet.

背景
诸多观察性研究已证实不饱和脂肪酸与银屑病之间存在关联，但此类研究均存在反向因果与混杂因素局限，且目前尚无针对不饱和脂肪酸与银屑病间因果关系的确定性研究。

研究目的
采用孟德尔随机化（Mendelian randomization）方法分析不饱和脂肪酸与银屑病之间的因果关联。

研究方法
本研究依托IEU开放全基因组关联研究（GWAS, Genome-Wide Association Study）项目数据库，纳入114999名受试者的ω-3多不饱和脂肪酸（PUFA, Polyunsaturated Fatty Acid）、ω-6多不饱和脂肪酸数据，13535名受试者的单不饱和脂肪酸（MUFA, Monounsaturated Fatty Acid）数据，以及包含4510例银屑病患者与212242名对照的银屑病数据。本研究以逆方差加权（IVW, Inverse-Variance Weighted）法作为主要分析手段，同时辅以4种孟德尔随机化分析方法。此外，分别采用Cochrane Q检验与MR-Egger截距检验完成异质性与水平多效性评估；最后通过敏感性分析提升研究结果的精准性与可靠性。

研究结果
逆方差加权分析结果显示：ω-3多不饱和脂肪酸对银屑病无因果作用（p=0.334；比值比（OR, Odds Ratio）=0.909；95%置信区间（CI, Confidence Interval）=0.748~1.104）；ω-6多不饱和脂肪酸可升高银屑病发病风险（p=0.046；OR=1.174；95%CI=1.003~1.374），单不饱和脂肪酸亦可升高银屑病发病风险（p=0.032；OR=1.218；95%CI=1.018~1.457）。反向因果分析显示，银屑病对ω-3多不饱和脂肪酸无因果影响（p=0.695；OR=0.989；95%CI=0.937~1.044），银屑病对ω-6多不饱和脂肪酸无因果影响（p=0.643；OR=1.013；95%CI=0.960~1.068），银屑病对单不饱和脂肪酸无因果作用（p=0.986；OR=1.000；95%CI=0.949~1.055）。异质性检验、水平多效性检验及敏感性分析结果均证实本研究结论可靠。

研究结论
本研究发现循环中ω-6多不饱和脂肪酸与单不饱和脂肪酸可诱导银屑病发病，而ω-3多不饱和脂肪酸无此效应；降低循环ω-6多不饱和脂肪酸与单不饱和脂肪酸水平的治疗方案可有效干预银屑病。在充分明确脂肪酸摄入与循环脂肪酸水平的关联机制后，可向目标人群提供饮食调控建议。