2型糖尿病与阿尔茨海默病之间的因果关联：一项两样本孟德尔随机化研究。
Causal Association Between Type 2 Diabetes Mellitus and Alzheimer's Disease: A Two-Sample Mendelian Randomization Study.
作者信息
Li Cong, Qian Haifeng, Feng Lina, Li Mingquan
机构信息
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
Department of Image Center, the Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, China.
出版信息
J Alzheimers Dis Rep. 2024 Jun 18;8(1):945-957. doi: 10.3233/ADR-240053. eCollection 2024.
BACKGROUND
There is now increasing evidence that type 2 diabetes mellitus (T2DM) is associated with Alzheimer's disease (AD). However, it is unclear whether the two are causally related.
OBJECTIVE
To reveal the causal association between T2DM and AD, we performed a bidirectional Mendelian randomization (MR) analysis.
METHODS
Genetic instrumental variables were systematically screened, and inverse-variance weighting, MR-Egger regression, weighted median, simple mode, and weighted mode were applied to assess the pathogenic associations between the two diseases, and sensitivity analyses were used to further validate the robustness of the results.
RESULTS
The results of forward MR analysis with T2DM as the exposure were [OR = 0.998, 95% CI (0.975∼1.021), = 0.857], and the results of reverse MR analysis with AD as the exposure were [OR = 0.966, 95% CI (0.934∼0.999), = 0.043]. The results showed no significant association between T2DM and AD at the gene level ( < 0.025). Sensitivity analyses were consistent with the results of the main analysis, confirming the robustness of the study.
CONCLUSIONS
T2DM and AD may not be genetically causally associated.
背景
现在越来越多的证据表明2型糖尿病（T2DM）与阿尔茨海默病（AD）有关。然而，两者是否存在因果关系尚不清楚。
目的
为了揭示T2DM与AD之间的因果关系，我们进行了双向孟德尔随机化（MR）分析。
方法
系统筛选遗传工具变量，应用逆方差加权、MR-Egger回归、加权中位数、简单模式和加权模式来评估两种疾病之间的致病关联，并使用敏感性分析进一步验证结果的稳健性。
结果
以T2DM为暴露因素的正向MR分析结果为[比值比（OR）=0.998，95%置信区间（CI）（0.975～1.021），P=0.857]，以AD为暴露因素的反向MR分析结果为[OR=0.966，95%CI（0.934～0.999），P=0.043]。结果显示，在基因水平上T2DM与AD之间无显著关联（P<0.025）。敏感性分析结果与主要分析结果一致，证实了本研究的稳健性。
结论
T2DM与AD可能不存在遗传因果关系。
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