孟德尔随机化
PI3K/AKT/mTOR通路
P70-S6激酶1
全基因组关联研究
肿瘤科
医学
蛋白激酶B
生物信息学
疾病
生物
遗传学
内科学
基因
信号转导
基因型
单核苷酸多态性
遗传变异
作者
Hong-Yan Cai,Shiyu Hou,Rui Wen,Qi-fan Feng,Yujia Xi,Sheng‐Xiao Zhang,Jun Qiao,Mei‐Na Wu
摘要
Most previous studies supported that the mammalian target of rapamycin (mTOR) is over-activated in Alzheimer's disease (AD) and exacerbates the development of AD. It is unclear whether the causal associations between the mTOR signaling-related protein and the risk for AD exist.This study aims to investigate the causal effects of the mTOR signaling targets on AD.We explored whether the risk of AD varied with genetically predicted AKT, RP-S6K, EIF4E-BP, eIF4E, eIF4A, and eIF4G circulating levels using a two-sample Mendelian randomization analysis. The summary data for targets of the mTOR signaling were acquired from published genome-wide association studies for the INTERVAL study. Genetic associations with AD were retrieved from the International Genomics of Alzheimer's Project. We utilized the inverse variance weighted as the primary approach to calculate the effect estimates.The elevated levels of AKT (OR = 0.910, 95% CI=0.840-0.986, p = 0.02) and RP-S6K (OR = 0.910, 95% CI=0.840-0.986, p = 0.02) may decrease the AD risk. In contrast, the elevated eIF4E levels (OR = 1.805, 95% CI=1.002-1.174, p = 0.045) may genetically increase the AD risk. No statistical significance was identified for levels of EIF4-BP, eIF4A, and eIF4G with AD risk (p > 0.05).There was a causal relationship between the mTOR signaling and the risk for AD. Activating AKT and RP-S6K, or inhibiting eIF4E may be potentially beneficial to the prevention and treatment of AD.
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