School of Nursing and Health, Zhengzhou University, High-Tech Development Zone of States, Zhengzhou 450001, P.R. China.
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, High-Tech Development Zone of States, Zhengzhou 450001, P.R. China.
Aging (Albany NY). 2020 Nov 7;12(21):21747-21757. doi: 10.18632/aging.103983.
Alzheimer's disease (AD) is a progressive brain disorder characterized by cognitive skills deterioration that affects many elderly individuals. The identified genetic loci for AD failed to explain the large variability in AD and very few causal factors have been identified so far.
mvMR showed that increasing years of schooling (OR=0.674, 95%CI: 0.571-0.796, =3.337E-06) and genetically elevated HDL cholesterol (OR ranging from 0.697 to 0.830, =6.940E-10) were inversely associated with AD risk, genetically predicted total cholesterol (OR=1.300, 1.196 to 1.412; =6.223E-10) and LDL cholesterol (OR=1.193, 1.097 to 1.296, =3.564E-05) were associated with increasing AD risk. Genetically predicted FG was suggestively associated with increased AD risk. Furthermore, MR-BMA analysis also confirmed FG and years of schooling as two of the top five causal risk factors for AD.
Our findings might provide us novel insights for treatment and intervention into the causal risk factors for AD or AD-related complex diseases.
By using extension methods of Mendelian randomization (MR)--multivariable MR (mvMR) and MR based on Bayesian model averaging (MR-BMA), we intend to estimate the potential causal relationship between nine risk factors and AD outcome and try to prioritize the most causal risk factors for AD.
阿尔茨海默病（AD）是一种进行性脑疾病，其特征是认知能力恶化，影响许多老年人。已确定的 AD 遗传位置未能解释 AD 的巨大变异性，迄今为止仅发现了极少数的致病因素。
mvMR 表明，受教育年限增加（OR=0.674，95%CI：0.571-0.796，=3.337E-06）和遗传上升高的高密度脂蛋白胆固醇（OR 范围为 0.697 至 0.830，=6.940E-10）与 AD 风险呈负相关，遗传预测的总胆固醇（OR=1.300，1.196-1.412；=6.223E-10）和 LDL 胆固醇（OR=1.193，1.097-1.296，=3.564E-05）与 AD 风险增加相关。遗传预测的 FG 与 AD 风险增加呈显著相关。此外，MR-BMA 分析还证实 FG 和受教育年限是 AD 的五个主要因果风险因素中的两个。
我们的研究结果可能为 AD 或 AD 相关复杂疾病的治疗和干预提供新的见解。
通过使用孟德尔随机化（MR）的扩展方法——多变量 MR（mvMR）和基于贝叶斯模型平均的 MR（MR-BMA），我们旨在估计 9 个风险因素与 AD 结局之间的潜在因果关系，并尝试确定 AD 的最主要因果风险因素。
