Zhu Haoning, Ni Huitong, Yang Qiuling, Ni Jiaqi, Ji Jianguang, Yang Shu, Peng Fu
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Int J Mol Sci. 2025 Apr 10;26(8):3589. doi: 10.3390/ijms26083589.
This study systematically evaluates and meta-analyzes Mendelian randomization studies on the bidirectional causal relationship between Alzheimer's disease (AD) and systemic diseases. We searched five databases, assessed study quality, and extracted data. Diseases were classified using ICD-11, and the meta-analysis was performed with RevMan 5.4. A total of 56 studies identified genetic links between AD susceptibility and systemic diseases. Notably, genetic proxies for hip osteoarthritis (OR = 0.80; = 0.007) and rheumatoid arthritis (OR = 0.97; = 0.004) were inversely associated with AD risk, while gout (OR = 1.02; = 0.049) showed a positive association. Genetic liability to depression (OR = 1.03; = 0.001) elevated AD risk, and AD genetic risk increased susceptibility to delirium (OR = 1.32; = 0.0005). Cardiovascular traits, including coronary artery disease (OR = 1.07; = 0.021) and hypertension (OR = 4.30; = 0.044), were causally linked to a higher AD risk. Other conditions, such as insomnia, chronic periodontitis, migraine, and certain cancers, exhibited significant genetic correlations. Intriguingly, herpes zoster (OR = 0.87; = 0.005) and cataracts (OR = 0.96; = 0.012) demonstrated inverse genetic associations with AD. These findings suggest potential therapeutic targets and preventive strategies, emphasizing the need to address comorbid systemic diseases to reduce AD risk and progression.
本研究系统地评估并荟萃分析了关于阿尔茨海默病（AD）与全身性疾病之间双向因果关系的孟德尔随机化研究。我们检索了五个数据库，评估了研究质量，并提取了数据。使用国际疾病分类第11版（ICD - 11）对疾病进行分类，并使用RevMan 5.4进行荟萃分析。总共56项研究确定了AD易感性与全身性疾病之间的遗传联系。值得注意的是，髋骨关节炎（比值比[OR]=0.80；P = 0.007）和类风湿性关节炎（OR = 0.97；P = 0.004）的遗传代理与AD风险呈负相关，而痛风（OR = 1.02；P = 0.049）则呈正相关。抑郁症的遗传易感性（OR = 1.03；P = 0.001）增加了AD风险，而AD遗传风险增加了谵妄易感性（OR = 1.32；P = 0.0005）。心血管特征，包括冠状动脉疾病（OR = 1.07；P = 0.021）和高血压（OR = 4.30；P = 0.044），与较高的AD风险存在因果关系。其他病症，如失眠、慢性牙周炎、偏头痛和某些癌症，表现出显著的遗传相关性。有趣的是，带状疱疹（OR = 0.87；P = 0.005）和白内障（OR = 0.96；P = 0.012）与AD呈反向遗传关联。这些发现提示了潜在的治疗靶点和预防策略，强调了应对合并全身性疾病以降低AD风险和进展的必要性。
