| 孔垂嘉,张影,谭振昆,平军娇,张海波,章杰,罗佳丽,刘新霞.痛风与阿尔茨海默病的因果关系：一项双样本孟德尔随机化分析[J].四川精神卫生杂志,2025,(2):115-122.Kong Chuijia,Zhang Ying,Tan Zhenkun,Ping Junjiao,Zhang Haibo,Zhang Jie,Luo Jiali,Liu Xinxia,Causal relationship between gout and Alzheimer's disease： a two-sample Mendelian randomization analysis[J].SICHUAN MENTAL HEALTH,2025,(2):115-122 |
| 痛风与阿尔茨海默病的因果关系：一项双样本孟德尔随机化分析 |
| Causal relationship between gout and Alzheimer's disease： a two-sample Mendelian randomization analysis |
| 投稿时间：2024-07-15 |
| DOI：10.11886/scjsws20240715001 |
| 中文关键词: 孟德尔随机化分析 痛风 阿尔茨海默病 因果关系 |
| 英文关键词:Mendelian randomization analysis Gout Alzheimer's disease Causality |
| 基金项目:2022年度中山市第三批社会公益与基础研究项目（医疗卫生）（项目名称：中山市居民抑郁情绪和认知损害早期筛查及干预措施研究，项目编号：2022B3017） |
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| 中文摘要: |
| 背景 痴呆严重影响老年人生活质量和寿命，阿尔茨海默病（AD）是最常见的痴呆类型。既往研究表明，痛风可能会降低AD的发病风险，但两者的因果关系仍需进一步研究。目的 采用双样本孟德尔随机化（MR）分析探讨痛风与AD之间的潜在因果关系，为AD的预防和治疗提供参考。方法 采用全基因组关联研究（GWAS）中，来自英国生物银行2021年发布的痛风（病例组6 810例，对照组477 788例）汇总数据作为暴露因素，FinnGen同年发布的AD（病例组3 899例，对照组214 893例）汇总数据作为结局指标。采用逆方差加权法、MR-Egger法、加权中位数法、简单模式法和加权模式法分析痛风与AD之间的潜在因果关系。使用MR-Egger法检测多效性，使用Cochran’s Q检验评估结果的异质性，使用留一法进行敏感性分析，绘制漏斗图检测偏倚性。结果 逆方差加权法显示，痛风与AD存在因果关系（OR=0.004，95% CI：0~0.700，P<0.05）。漏斗图显示，两侧的SNP分布基本对称，因果关系受潜在偏倚影响的可能性较小。Cochran’s Q检验结果显示，痛风与AD的MR分析异质性无统计学意义。MR-Egger法结果表明，痛风的工具变量间不存在水平多效性。痛风与AD的反向MR分析结果表明，痛风与AD无反向因果关系。结论 痛风是AD的保护因素，痛风可能会降低AD的发病风险。 |
| 英文摘要: |
| Background Dementia seriously affects the quality of life and lifespan of elderly people， with Alzheimer's disease （AD） being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD， but the causal relationship between the two still requires further research.Objective To investigate the potential causal relationship between gout and AD through a two-sample Mendelian randomization （MR） analysis， so as to provide references for the prevention and treatment of AD.Methods Data from Genome-Wide Association Studies （GWAS） extracted in 2024 were analyzed， using pooled data on gout （6 810 cases in the case group and 477 788 cases in the control group） published by UK Biobank in 2021 as the exposure variable， and data on AD （3 899 cases in the case group and 214 893 cases in the control group） published by FinnGen in the same year as the outcome variable. The inverse-variance weighted， MR-Egger regression， weighted median estimation， simple model and weighted model were used to analyze the potential causal relationship between gout and AD. Pleiotropic effects were assessed using MR-Egger regression. Heterogeneity assessment was conducted using Cochran's Q test. The leave-one-out analysis was carried out for sensitivity analysis. And a funnel plot was drawn to detect potential publication bias.Results The inverse-variance weighted analysis demonstrated a negative causal relationship between gout and AD （OR=0.004， 95% CI： 0~0.700， P<0.05）. The plot resembled a symmetrical inversed funnel， indicating the absence of publication bias. No heterogeneity was detected by Cochran's Q test. The MR-Egger regression indicated no significant horizontal pleiotropy. Concerning the reverse directions， no significant associations between AD and gout were noted.Conclusion There is a negative causal relationship between gout and AD， with gout potentially reducing the risk of developing AD. ［Funded by The Third Batch of Social Welfare and Basic Research Projects （Medical and Health） of Zhongshan City in 2022 （number， 2022B3017）］ |
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