睾酮对阿尔茨海默病影响的中介作用：脂质代谢和肥胖：一项孟德尔随机研究。

The Impact of Testosterone on Alzheimer's Disease Are Mediated by Lipid Metabolism and Obesity: A Mendelian Randomization Study.

机构信息

Lin Yang, Xi'an Hospital of Traditional Chinese Medicine, Shaanxi, China,

出版信息

J Prev Alzheimers Dis. 2024;11(2):507-513. doi: 10.14283/jpad.2023.116.

DOI:10.14283/jpad.2023.116

PMID:38374757

Abstract

BACKGROUND

To investigate the causal relationship between testosterone (BT) levels and Alzheimer's disease (AD) risk and to quantify the role of obesity and lipid metabolism as potential mediators.

METHODS

We used a two-sample, two-step MR to determine:1) the causal effect of BT levels on AD; 2) the causal effect of two lipid metabolites, obesity and LDLc on AD; and 3) the mediating effects of these metabolites. Pooled data for BT levels and lipid metabolism were obtained from the UK Biobank. AD data were obtained from the Alzheimer's Disease Project International Genomics Consortium, FinnGen Consortium, and UK Biobank study. Effect estimates from external genome-wide association study (GWAS) pooled statistics were obtained using inverse variance-weighted (IVW) MR analysis.

RESULTS

Higher levels of BT were associated with a reduced risk of AD (odds ratio [OR] 0.9992, 95% CI 0.9985-0.9998, P = 0.019), and there was a negative correlation with LDLc (OR 0.9208, 95% CI 0.8569-0.9895, P = 0.024) and obesity class 2 (OC2) (OR 0.7445, 95% CI 0.5873-0.9437, P = 0.014). Conversely, there was a positive correlation between LDLc (OR 1.0014, 95% CI 1.0000-1.0029, P = 0.043) and OC2 (OR 1.0005, 95% CI 1.0001-1.0009, P = 0.003) and AD. Mediation analysis showed that the indirect effect of BT levels on AD was achieved through LDLc and OC2, which accounted for 17% and 17% of the total effect, respectively.

CONCLUSION

Our study identified a causal role of BT levels in LDLc and OC2. BT levels may affect AD through LDLc and OC2 metabolic processes.

摘要

背景

为了探究睾酮（BT）水平与阿尔茨海默病（AD）风险之间的因果关系，并定量评估肥胖和脂质代谢作为潜在中介因素的作用。

方法

我们采用两样本、两步孟德尔随机化（MR）方法来确定：1）BT 水平对 AD 的因果效应；2）两种脂质代谢物，肥胖和 LDLc 对 AD 的因果效应；以及 3）这些代谢物的中介作用。BT 水平和脂质代谢的汇总数据来自英国生物库。AD 数据来自阿尔茨海默病项目国际基因组联盟、芬兰基因联盟和英国生物库研究。使用逆方差加权（IVW）MR 分析从外部全基因组关联研究（GWAS）汇总统计数据中获得效应估计值。

结果

较高的 BT 水平与 AD 风险降低相关（比值比 [OR] 0.9992，95%置信区间 [CI] 0.9985-0.9998，P = 0.019），并且与 LDLc（OR 0.9208，95%CI 0.8569-0.9895，P = 0.024）和肥胖 2 级（OC2）（OR 0.7445，95%CI 0.5873-0.9437，P = 0.014）呈负相关。相反，LDLc（OR 1.0014，95%CI 1.0000-1.0029，P = 0.043）和 OC2（OR 1.0005，95%CI 1.0001-1.0009，P = 0.003）与 AD 呈正相关。中介分析表明，BT 水平对 AD 的间接效应是通过 LDLc 和 OC2 实现的，它们分别占总效应的 17%和 17%。