Li Ya Jia, Li Qiang Xiang, Cao Zi Qin, Wu Jian Huang
Department of Dermatology, Xiangya Hospital, Central South University, Changsha 410011, Hunan, China;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Biomed Environ Sci. 2025 Mar 20;38(3):365-375. doi: 10.3967/bes2024.122.
To explore the causality between reproductive traits and risk of psoriasis by using a large Mendelian randomization (MR) study.
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).
Genetically predicted early age at first sexual intercourse (AFS) led to an increased risk of overall psoriasis [odds ratio ( ) : 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 ( : 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.
Early AFB may cause a higher risk of PsA, while the AFS-PsA association was fully mediated by BMI.
通过一项大型孟德尔随机化（MR）研究探讨生殖特征与银屑病风险之间的因果关系。
采用两样本MR研究，使用生殖特征全基因组关联研究（GWAS）的汇总统计数据，以及关于总体银屑病、银屑病关节炎（PsA）和寻常型银屑病（PV）的GWAS数据。除单变量MR（UVMR）外，还使用多变量MR和两步MR来计算独立效应，并量化教育或体重指数（BMI）介导的比例。
基因预测的首次性交年龄（AFS）较早会导致总体银屑病风险增加[优势比（OR）：0.54]；这种效应的36.13%通过BMI介导，47.79%通过教育程度介导。首次生育年龄（AFB）与PsA之间的直接负向因果关联占主导（OR：0.76），其中49.61%的中介作用归因于BMI。发现BMI对AFS与PV的关系有中介作用，占比例的26.27%。AFS与总体银屑病和PV的风险呈负相关，BMI和教育程度起了相当大的中介作用。
AFB较早可能导致PsA风险较高，而AFS与PsA的关联完全由BMI介导。
