Gout and the risk of Alzheimer′s disease: A Mendelian randomization study
Gout and the risk of Alzheimer′s disease: A Mendelian randomization study
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DOI：
10.1111/1756-185x.13548
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发表时间：
2019-06-01
影响因子：
2.5
通讯作者：
Lee, Young Ho
中科院分区：
文献类型：
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作者：
Lee, Young Ho
目的探讨痛风与阿尔茨海默病的关系。方法我使用公开可用的三个全基因组关联研究（GWASs）的汇总统计数据集作为暴露数据集，并使用由17 008例阿尔茨海默病患者和37 154例欧洲血统对照组成的4个GWASs数据集的荟萃分析结果作为结果数据集。数据进行2样本孟德尔随机化（MR）分析，使用逆方差加权（IVW），加权中位数，和MR-Egger回归方法。结果我从痛风GWAS中选择了7个独立的单核苷酸多态性（SNPs）作为工具变量（IVs），以改善推断。这些SNP位于MAP 3 K11（rs 10791821）、SLC 2A 9（rs 11722228、rs734553）、GCKR（rs 1260326）、ABCG 2（rs 2231142、rs 2728125）和CNIH-2（rs 4073582）。IVW数据不支持痛风和阿尔茨海默病之间的因果关系（β = 0.013，标准误[SE] = 0.017，P = 0.445）。MR-Egger回归分析表明，方向性多效性不会使结果产生偏倚（截距= 0.002，P = 0.654）;它还表明痛风和阿尔茨海默病之间没有因果关系（β =-0.013，SE = 0.076，P = 0.870）。加权中位数方法得出了相似的结果（β = 0.004，SE = 0.022，P = 0.846）。Cochran’s Q检验表明，基于个体变异的IV估计值之间没有异质性的证据，“留一法”分析的结果表明，没有单一SNP驱动IVW估计值。结论磁共振分析结果不支持痛风和阿尔茨海默病之间的因果关系。
Objective This study aimed to examine whether gout is causally associated with Alzheimer's disease. Methods I used the publicly available summary statistics datasets of three genome-wide association studies (GWASs) on gout as the exposure dataset and meta-analysis results of four GWAS datasets consisting of 17 008 cases with Alzheimer's disease and 37 154 controls of European descent as the outcome dataset. The data were subjected to 2-sample Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW), weighted median, and MR-Egger regression methods. Results I selected seven independent single nucleotide polymorphisms (SNPs) from gout GWASs as instrumental variables (IVs) to improve inference. These SNPs were located at MAP3K11 (rs10791821), SLC2A9 (rs11722228, rs734553), GCKR (rs1260326), ABCG2 (rs2231142, rs2728125), and CNIH-2 (rs4073582). The IVW data did not support a causal association between gout and Alzheimer's disease (beta = 0.013, standard error [SE] = 0.017, P = 0.445). The MR-Egger regression indicated that directional pleiotropy did not bias the result (intercept = 0.002, P = 0.654); it also revealed no causal association between gout and Alzheimer's disease (beta = -0.013, SE = 0.076, P = 0.870). The weighted median approach yielded similar results (beta = 0.004, SE = 0.022, P = 0.846). Cochran's Q test indicated no evidence of heterogeneity between IV estimates based on individual variants, and the results of "leave-one-out" analysis demonstrated that no single SNP drove the IVW estimate. Conclusions The MR analysis results did not support a causal association between gout and Alzheimer's disease.