瘦素作为遗传预测的银屑病与心肌梗死之间的潜在中介因素:一项网络孟德尔随机化研究

Leptin as A Potential Mediator of Genetically Predicted Psoriasis with Myocardial Infarction:A Network Mendelian Randomization Study

目的运用网络孟德尔随机化(MR)研究评估遗传预测的银屑病与心肌梗死(MI)之间的因果关系,以及瘦素作为潜在中介因素的作用。方法这是一项利用全基因组关联分析进行网络MR的研究。网络MR被用于评估银屑病与MI之间的关联,采用中介分析估计瘦素作为遗传预测的银屑病与MI之间的潜在中介因素。结果本研究表明,遗传预测的银屑病与MI有关联(OR=1.004,95%CI 1.001~1.008,P=0.044),在FinnGen验证数据集中也得到了确认(OR=1.006,95%CI 1.001~1.012,P=0.025),该结果也在汇总的荟萃分析中被证实(OR=1.005,95%CI 1.002~1.008,P<0.001)。进一步的中介分析表明,遗传预测的银屑病也与瘦素有关(β=0.003,SE=0.001,P=0.047)。此外,瘦素水平每增加一个单位,MI的风险增加13.1%(OR=1.131,95%CI 1.007~1.269,P=0.037)。结论本研究提供的证据表明银屑病与MI密切相关,可能通过瘦素介导,干预瘦素可能有助于降低银屑病患者MI的发病率。

Objective The network Mendelian randomization(MR)study aimed to assess the causal relationship of genetically predicted psoriasis with myocardial infarction(MI),as well as the role of leptin as a potential mediator.Methods This was a network MR study that utilized genome-wide association study.Network MR was used to evaluate the association between psoriasis and MI,and mediation analysis was used to estimate leptin as a potential mediator for genetically predicted psoriasis with MI.Results This findings indicated that genetically predicted psoriasis was associated with MI(OR=1.004,95%CI 1.001~1.008,P=0.044),which was confirmed in the FinnGen validation dataset(OR=1.006,95%CI 1.001~1.012,P=0.025),as well as in the pooled meta-analysis(OR=1.005,95%CI 1.002~1.008,P<0.001).Further mediation analysis suggested that genetically predicted psoriasis was also associated with leptin(β=0.003,SE=0.001,P=0.047).Moreover,for every unit increased in leptin levels,the risk of MI increased by 13.1%(OR=1.131,95%CI 1.007~1.269,P=0.037).Conclusion This study provided evidence that psoriasis was closely associated with MI,which may be mediated by leptin.Intervention with leptin may help to reduce the incidence of MI in patients with psoriasis.