血浆尿酸水平与多种慢性病及其指标的因果关系分析

    Causal relationship between plasma uric acid level and many chronic diseases and their parameters

    • 摘要:
      目的  关于血尿酸(serum uric acid,SUA)水平与心血管疾病和代谢性疾病相关的研究很多,但其与这些慢性疾病是否存在因果关系尚不清楚。本研究旨在探讨SUA与多种慢性疾病之间的因果关系。
      方法  采用逆方差加权法(inverse variance weighted,IVW)、MR-Egger回归法、加权中位数法(weighted median,WM)、简单模式法和加权模式法进行孟德尔随机化(mendelian randomization,MR)分析。选取东亚人群的全基因组关联分析数据集,以SUA水平数据作为暴露因素,以冠心病(coronary artery disease,CAD)、收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心房颤动 (atrial fibrillation,AF)、Ⅱ型糖尿病 (diabetes mellitus type 2,T2DM)、慢性阻塞性肺部疾病 (chronic obstructive pulmonary disease,COPD)、充血性心力衰竭 (congestive heart failure,CHF)、缺血性中风 (ischemic stroke,IS)、骨质疏松症 (osteoporosis,OP) 和外周动脉疾病 (peripheral artery disease,PAD) 数据作为结局。进行MR分析和敏感性分析,通过对数据进行异质性检验、水平多效性检验和留一法检验结果的稳健性。
      结果  SUA水平与CAD(OR = 1.240,95% CI:1.1521.335,P < 0.001)、DBP(OR = 1.074,95% CI:1.0301.120,P < 0.001)、MAP(OR = 1.050,95% CI:1.0161.086,P = 0.004)和CHF(OR = 1.146,95% CI:1. 0321.274,P = 0.011)发病风险正相关,与SBP、AF、T2DM、COPD、IS、OP和PAD无因果关联。由于水平多效应的存在,SUA与CAD的因果关系并不稳健。
      结论  SUA水平与DBP、MAP和CHF之间存在正向因果关系,SUA水平升高增加DBP、MAP水平和CHF的风险。

       

      Abstract:
      Objective  Numerous studies focused upon the association of uric acid with cardiovascular and metabolic diseases. However, whether or not there are causal relationships with these chronic diseases has remained unclear. We conducted the study to explore the causal relationship between uric acid and various chronic diseases.
      Methods  Inverse variance weighting (IVW), MR-Egger regression, weighted median (WM), simple mode and weighted mode methods were utilized for Mendelian randomization (MR) analysis. The relevant data were obtained from the Genome-Wide Association Study (GWAS) pooled dataset with serum uric acid (SUA) levels as exposure and coronary artery disease (CAD), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), atrial fibrillation (AF), type 2 diabetes (T2D), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), ischemic stroke (IS), osteoporosis (OP) and peripheral artery disease (PAD) as outcomes in the East Asian population. Sensitivity analyses were also performed for examining the data robustness of the results through heterogeneity test, horizontal multiple validity test and leave-one-out methods.
      Results  SUA level had positive causal associations with CAD(OR=1.240, 95%CI: 1.152~1.335, P<0.001), DBP(OR=1.074, 95% CI: 1.030~1.120, P<0.001), MAP(OR =1.050, 95% CI: 1.016~1.086, P = 0.004)and CHF(OR = 1.146, 95% CI: 1.032~1.274, P = 0.011)and no causal associations with SBP, AF, T2D, COPD, IS, OP or PAD. However, the causal association of SUA with CAD was not robust due to the presence of horizontal pleiotropy.
      Conclusions  A positive causal relationship exists between SUA level and DBP, MAP and CHF. And an elevation of SUA level boosts the levels of DBP and MAP and the risk of CHF.

       

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