Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study.
Associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease: a Mendelian randomization study.
复制标题
DOI：
10.1038/s41398-023-02553-9
复制
发表时间：
2023-07-24
影响因子：
6.8
通讯作者：
Yu, Jin-Tai
中科院分区：
文献类型：
--
作者：
Huang, Liang-Yu;Ou, Ya-Nan;Yang, Yu-Xiang;Wang, Zuo-Teng;Tan, Lan;Yu, Jin-Tai
以前的观察性研究报告了心血管危险因素和生活方式行为的中年聚集性与神经退行性疾病相关；然而，这些发现可能被混淆和反向因果关系所偏颇。本研究采用两样本孟德尔随机设计，研究心血管危险因素和生活方式与神经退行性疾病之间的因果关系。可改变的危险因素和神经退行性疾病的遗传变异是从大规模的全基因组关联研究中提取的。使用逆方差加权方法作为主要分析方法，并进行MR-Egger回归和留一分析以识别潜在的违规行为。基因预测的舒张压(DBP：OR每1 汞，0.990[0.979-1.000])、体重指数(BMI：OR每1 SD，0.880[0.825-0.939])和教育水平(OR每1 SD，0.698[0.602-0.810])与晚发性阿尔茨海默病(LOAD)的风险降低有关，而基因预测的低密度脂蛋白(LDLOR：OR PER 1 SD，1.302[1.066-1.590])可能增加晚发性阿尔茨海默病(LOAD)的风险。遗传预测的暴露(包括低密度脂蛋白和体重指数)应用于家族性阿尔茨海默病，显示出同样的效果。低密度脂蛋白与肌萎缩侧索硬化症也有关联(低密度脂蛋白：或每1 SD，1.180[1.080-1.289])。这项MR分析表明，低密度脂蛋白、体重指数、血压和教育水平与AD有因果关系；低密度脂蛋白与ALS风险显著相关，以及睡眠时间对帕金森病风险的潜在影响。以这些可改变的因素为靶点是神经退行性疾病预防的一个很有前途的策略。
Previous observational studies reported that midlife clustering of cardiovascular risk factors and lifestyle behaviors were associated with neurodegenerative disease; however, these findings might be biased by confounding and reverse causality. This study aimed to investigate the causal associations of cardiovascular risk factors and lifestyle behaviors with neurodegenerative disease, using the two-sample Mendelian randomization design. Genetic variants for the modifiable risk factors and neurodegenerative disease were extracted from large-scale genome-wide association studies. The inverse-variance weighted method was used as the main analysis method, and MR-Egger regression and leave-one-out analyses were performed to identify potential violations. Genetically predicted diastolic blood pressure (DBP: OR per 1 mmHg, 0.990 [0.979–1.000]), body mass index (BMI: OR per 1 SD, 0.880 [0.825–0.939]), and educational level (OR per 1 SD, 0.698 [0.602–0.810]) were associated with lower risk of late-onset Alzheimer’s disease (LOAD), while genetically predicted low-density lipoprotein (LDL: OR per 1 SD, 1.302 [1.066–1.590]) might increase LOAD risk. Genetically predicted exposures (including LDL and BMI) applied to familial AD showed the same effect. The association of LDL was also found with Amyotrophic lateral sclerosis (ALS) (LDL: OR per 1 SD, 1.180 [1.080–1.289]). This MR analysis showed that LDL, BMI, BP, and educational level were causally related to AD; a significant association between LDL and ALS risk, as well as the potential effect of sleep duration on PD risk, were also revealed. Targeting these modifiable factors was a promising strategy of neurodegenerative disease prevention.
登录
查看更多内容
影响因子：
120.7
作者：
Lieb, Wolfgang;Beiser, Alexa S.;Vasan, Ramachandran S.;Tan, Zaldy S.;Au, Rhoda;Harris, Tamara B.;Roubenoff, Ronenn;Auerbach, Sanford;DeCarli, Charles;Wolf, Philip A.;Seshadri, Sudha
通讯作者：
Seshadri, Sudha
影响因子：
4.4
作者：
Blume, Josefine;Rothenfusser, Eva;Lange, Max
通讯作者：
Lange, Max
影响因子：
9.9
作者：
Huang J;Zuber V;Matthews PM;Elliott P;Tzoulaki J;Dehghan A
通讯作者：
Dehghan A
DOI：
10.1016/j.dadm.2017.05.007
发表时间：
2017
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
Albanese E;Launer LJ;Egger M;Prince MJ;Giannakopoulos P;Wolters FJ;Egan K
通讯作者：
Egan K
影响因子：
48
作者：
Lane, Christopher A.;Barnes, Josephine;Schott, Jonathan M.
通讯作者：
Schott, Jonathan M.