血清代谢物与银屑病的风险——一项两样本孟德尔随机化研究

Serum Metabolites and the Risk of Psoriasis:A Two-Sample Mendelian Randomization Study

目的探究血清代谢物对银屑病发病风险的影响。方法运用孟德尔随机化(Mendelian randomization,MR)方法评估486种血清代谢物与银屑病发病风险之间的关联,因果效应主要以逆方差加权法(inverse-variance weighted,IVW)的P值、优势比(odds ratio,OR)和95%置信区间(confidence intervals,CI)进行评估。采用错误发现率(false discovery rate,FDR)进行多重比较,采用IVW、MR-多效性残差和异常值法(MR pleiotropy RESidual sum and outlier,MR-PRESSO)进行敏感性分析,并进行反向因果关系检验及代谢途径富集分析。结果IVW结果共发现28种与银屑病风险相关的血清代谢物,11种已知,17种未知。因果效应最强的保护性及危险性代谢产物分别为1-棕榈酰基甘油磷胆碱(OR=0.06,95%CI:0.01~0.70,P_(IVW)=0.02,P_(FDR)=0.29),肌酸(OR=3.67,95%CI:1.40~9.61,P_(IVW)=0.01,P_(FDR)=0.28)。各项敏感性分析结果稳健,结果不存在异质性、多效性及反向因果关系。代谢途径主要富集于谷胱甘肽代谢及氨基酸代谢。结论血清代谢产物与银屑病发病风险存在因果关系,其中5-氧代脯氨酸、2-氨基丁酸等9种代谢物水平的升高可能与银屑病发病风险的降低相关,而肌酸、色氨酸甜菜碱水平的升高可能增加银屑病患病风险。

Objective To investigate the impact of serum metabolites on the risk of psoriasis.Methods Mendelian randomization(MR)analysis was used to evaluate the association between 486 serum metabolites and the risk of psoriasis.The causal effects were mainly evaluated using the P-value,odds ratio(OR),and 95%confidence interval(CI)of the inverse variance weighted(IVW)method.Multiple comparisons were conducted using false discovery rate(FDR),sensitivity analysis was performed using IVW,MR-PRESSO,etc.Reverse causality was tested and enrichment analysis was performed on metabolic pathways.Results The IVW results revealed a total of 28 serum metabolites associated with psoriasis risk,of which 11 were known and 17 were unknown.The most protective and dangerous metabolites with the strongest causal effects respectively were 1-palmitoylglycophorophosphocline(OR=0.06,95%CI:0.01-0.70,P_(IVW)=0.02,P_(FDR)=0.29)and creatine(OR=3.67,95%CI:1.40-9.61,P_(IVW)=0.01,P_(FDR)=0.28).The sensitivity analysis results were robust,indicating that there were no heterogeneity,pleiotropy,or reverse causality in the results.The metabolic pathways of metabolites were mainly enriched in glutathione metabolism and amino acid metabolism.Conclusion There is a causal relationship between serum metabolites and the risk of psoriasis.Among them,the increased levels of 9 metabolites,including 5-oxoproline,2-aminobutyrat and hexanoylcarnitine,may be related to the decreased risk of psoriasis.The increase of creatine and tryptophan betaine levels may increase the risk of psoriasis.