摘要Objective To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization(MR)study.Methods A two-sample MR study was performed using summarized statistics from the genome-wide association studies(GWAS)conducted in reproductive traits,as well as GWAS data on overall psoriasis,psoriatic arthritis(PsA),and psoriasis vulgaris(PV).Besides univariable MR(UVMR),multivariable MR and two-step MR was used to calculate the independent effects and quantify the proportion mediated by education or body mass index(BMI).Results Genetically predicted early age at first sexual intercourse(AFS)led to an increased risk of overall psoriasis[odds ratio(OR)UVMR:0.54];36.13%of this effect was mediated through BMI and 47.79%through educational attainment.The direct negative casual association between age at first birth(AFB)-PsA was dominant(ORUVMR:0.76),with 49.61%proportion of the mediation due to BMI.The mediating effect was found for BMI on the AFS-PV relationship,which accounted for 26.27%of the proportion.AFS was inversely associated with the risk of overall psoriasis and PV,with considerable mediation by BMI and educational attainment.Conclusion Early AFB may cause a higher risk of PsA,while the AFS-PsA association was fully mediated by BMI.