可改变性危险因素与原发性胆汁性胆管炎之间的因果关系:一项全面的孟德尔随机化研究

Causal relationship between modifiable risk factors and primary biliary cholangitis:a comprehensive Mendelian randomization study

目的早期识别可改变性危险因素对于预防原发性胆汁性胆管炎(primary biliary cholangitis,PBC)至关重要。目前认为PBC的发病机制与环境和遗传因素密切相关。该研究旨在系统性探讨基因预测的可改变性危险因素与PBC之间的因果关系。方法孟德尔随机化(Mendelianrandomization,MR)分析可以作为一种流行病学方法来研究不同随机化与特定疾病之间的因果关系。在本研究中,我们使用单变量和多变量MR分析来探索133个基因预测的可改变性危险因素与PBC之间的因果关系。结果果我们发现,遗传预测的自恋、终生性伴侣的数量、失眠、血清中3-甲基组氨酸水平、血清中汞水平、血清白细胞中嗜酸性粒细胞百分比、冠心病、湿疹和全身脂肪重量(whole body fat mass,WFM)与PBC风险增加有因果性关联(P值均<0.05)。另外,基因预测的认知表现、神经过敏症、大专以上学历、血清中甘氨酸水平、血清中羟脯氨酸水平、血清中C反应蛋白水平、血清中牛磺酸水平以及站立身高与PBC风险降低有潜在关联(P值均<0.05)。在多变量MR分析(分别校正BMI和WFM因素后)中,血清白细胞中嗜酸性粒细胞百分比仍与PBC的风险增加相关,而认知表现仍与PBC的发生风险降低有潜在因果关系。结论总体而言,WFM和血清白细胞中嗜酸性粒细胞百分比是PBC的因果性危险因素,而基因预测的认知表现与PBC的发生风险较低相关。这意味着这些可改变性危险因素是预防PBC的重要目标。

Objective Early identification of modifiable risk factors is crucial for the prevention of primary biliary cholangitis(PBC).The pathogenesis of PBC is currently believed to be closely related to environmental and genetic factors.This study aims to systematically explore the causal relationship between modifiable risk factors predicted by genes and PBC.Methods Mendelian randomization(MR)analysis can be used as an epidemiological method to study the causal relationship between different randomizations and specific diseases.In this study,we used univariate and multivariate MR analysis to explore the causal relationship between modifiable risk factors predicted by 133 genes and PBC.Results We found that genetic prediction of narcissism,number of lifelong sexual partners,insomnia,serum 3-methyl histidine level,serum mercury level,serum eosinophil percentage in white blood cells,coronary heart disease,eczema and whole body fat mass(WFM)were causal associated with increased risk of PBC(all P values<0.05).In addition,genetic prediction of cognitive performance,neuroticism,college degree or above,serum glycine level,serum hydroxyproline level,serum C-reactive protein level,serum taurine level and standing height were potentially associated with reduced risk of PBC(all P values<0.05).In multivariate MR analysis(adjusted for BMI and WFM respectively),serum eosinophil percentage was stll associated with increased risk of PBC,while cognitive performance was still associated with a potential causal relationship with a lower risk of PBC.Conclusion WFM and serum eosinophil percentage are causal risk factors for PBC,while genetically predicted cognitive performance is associated with a lower risk of PBC.This means that these modifiable risk factors are important targets for the prevention of PBC.