Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, China.
J Alzheimers Dis. 2020;78(4):1679-1687. doi: 10.3233/JAD-200773.
Several studies have shown risky behaviors and risk tolerance are associated with Alzheimer's disease. However, the underlying causality remains unclear. Risky behavior and risk tolerance may induce the onset of Alzheimer's disease, and/or vulnerability to Alzheimer's disease may result in more risky behaviors.
To examine bidirectional relationships between risky behavior, risk tolerance, and Alzheimer's disease using Mendelian randomization method for assessing potential causal inference.
This bidirectional two-sample Mendelian randomization study used independent genetic variants associated with risky behaviors and risk tolerance (n = 370, 771- 939, 908), and Alzheimer's disease (n = 71, 880 - 37, 613) as genetic instruments from large meta-analyses of genome-wide association studies.
Our results support a strong protective casual effect of risk-taking tendency on AD (odds ratio [OR] = 0.79; 95% CI, 0.67- 0.94, p = 0.007). There was weak statistically significant relationship between number of sexual partners and AD (OR = 0.50, 95% CI, 0.27- 0.93, p = 0.04), and between family history of AD and automobile speeding propensity (OR = 1.018, 95% CI, 1.005 to 1.031; p = 0.007). Contrary to expectations, there was no statistically significant causal effect of AD on risk-taking tendency (β= 0.015, 95% CI, - 0.005 to 0.04; p = 0.14).
Under Mendelian randomization assumptions, our results suggest a protective relationship between risk-taking tendency and the risk of AD. This finding may provide valuable insights into Alzheimer's disease pathogenesis and the development of preventive strategies.
多项研究表明，危险行为和风险承受能力与阿尔茨海默病有关。然而，潜在的因果关系尚不清楚。危险行为和风险承受能力可能会引发阿尔茨海默病的发生，而阿尔茨海默病的易感性可能会导致更多的危险行为。
使用孟德尔随机化方法评估潜在的因果关系，检验危险行为、风险承受能力与阿尔茨海默病之间的双向关系。
这项双向两样本孟德尔随机化研究使用了来自全基因组关联研究荟萃分析的与危险行为和风险承受能力（n=370771-939，908）和阿尔茨海默病（n=71880-37，613）相关的独立遗传变异作为遗传工具。
我们的结果支持冒险倾向对 AD 有很强的保护作用（优势比[OR]为 0.79；95%置信区间，0.67-0.94，p=0.007）。性伴侣数量与 AD 之间存在微弱的统计学显著关系（OR=0.50，95%置信区间，0.27-0.93，p=0.04），AD 家族史与汽车超速倾向之间存在微弱的统计学显著关系（OR=1.018，95%置信区间，1.005-1.031；p=0.007）。与预期相反，AD 对冒险倾向没有统计学上显著的因果影响（β=0.015，95%置信区间，-0.005-0.04；p=0.14）。
在孟德尔随机化假设下，我们的结果表明冒险倾向与 AD 风险之间存在保护关系。这一发现可能为阿尔茨海默病的发病机制和预防策略的制定提供有价值的见解。
