Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease.
Mendelian randomization study shows no causal relationship between circulating urate levels and Parkinson's disease.
复制标题
孟德尔随机研究表明，循环尿酸盐水平与帕金森氏病之间没有因果关系。
DOI：
10.1002/ana.25294
复制
发表时间：
2018-08
影响因子：
11.2
通讯作者：
Wood NW
中科院分区：
文献类型：
--
作者：
Kia DA;Noyce AJ;White J;Speed D;Nicolas A;IPDGC collaborators;Burgess S;Lawlor DA;Davey Smith G;Singleton A;Nalls MA;Sofat R;Wood NW
观察性研究表明，血浆尿酸盐升高与帕金森病（PD）风险降低相关，但这些研究并非旨在检验因果关系。如果存在因果关系，那么调节血浆尿酸水平可能是PD的潜在预防途径。我们采用大样本孟德尔随机化（MR）设计来评估血浆尿酸盐与PD风险之间的因果关系。我们在病例对照全基因组关联研究数据集上使用了由31个独立的血浆尿酸盐位点组成的遗传工具，该数据集包括13，708例PD病例和95，282例对照。使用逆方差加权（IVW）方法合并每个SNP的个体效应估计值。另外两种方法，MR-Egger和基于惩罚加权中位数（PWM）的方法，用于评估归因于多效性或无效仪器的潜在偏倚。我们没有发现尿酸盐和PD之间存在因果关系的证据，根据IVW方法估计的效应比值比（OR）为1.03（95%置信区间[CI]，0.88-1.20），血浆尿酸盐水平每增加1个标准差。MR Egger和PWM分析得出了相似的估计值（OR分别为0.99 [95% CI，0.83-1.17]和0.99 [95% CI，0.86 - 1.14]）。我们没有发现尿酸盐对PD风险具有线性因果保护作用的证据。在先前的观察性研究中观察到的相关性可能部分归因于混杂或反向因果关系。在本研究的背景下，提高循环尿酸盐水平的策略可能不会降低总体PD风险。
Observational studies have shown that increased plasma urate is associated with lower risk of Parkinson’s disease (PD), but these studies were not designed to test causality. If a causal relationship exists, then modulating plasma urate levels could be a potential preventive avenue for PD. We used a large two-sample Mendelian randomization (MR) design to assess for a causal relationship between plasma urate and PD risk. We used a genetic instrument consisting of 31 independent loci for plasma urate on a case-control genome-wide association study data set, which included 13,708 PD cases and 95,282 controls. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. Two additional methods, MR-Egger and a penalized weighted median (PWM)-based approach, were used to assess potential bias attributed to pleiotropy or invalid instruments. We found no evidence for a causal relationship between urate and PD, with an effect estimate from the IVW method of odds ratio (OR) 1.03 (95% confidence interval [CI], 0.88–1.20) per 1-standard-deviation increase in plasma urate levels. MR Egger and PWM analyses yielded similar estimates (OR, 0.99 [95% CI, 0.83–1.17] and 0.99 [95% CI, 0.86−1.14], respectively). We did not find evidence for a linear causal protective effect by urate on PD risk. The associations observed in previous observational studies may be, in part, attributed to confounding or reverse causality. In the context of the present findings, strategies to elevate circulating urate levels may not reduce overall PD risk.
登录
查看更多内容
痛风与多发性硬化症，帕金森氏病和运动神经元疾病之间的临床关联：记录链接研究。
影响因子：
2.6
作者：
Pakpoor J;Seminog OO;Ramagopalan SV;Goldacre MJ
通讯作者：
Goldacre MJ
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
DOI：
10.1073/pnas.78.11.6858
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
AMES, BN;CATHCART, R;HOCHSTEIN, P
通讯作者：
HOCHSTEIN, P
影响因子：
30.8
作者：
Chang D;Nalls MA;Hallgrímsdóttir IB;Hunkapiller J;van der Brug M;Cai F;International Parkinson's Disease Genomics Consortium;23andMe Research Team;Kerchner GA;Ayalon G;Bingol B;Sheng M;Hinds D;Behrens TW;Singleton AB;Bhangale TR;Graham RR
通讯作者：
Graham RR
影响因子：
7.7
作者：
Lawlor DA
通讯作者：
Lawlor DA