Wang Rong-Ze, Yang Yu-Xiang, Li Hong-Qi, Shen Xue-Ning, Chen Shi-Dong, Cui Mei, Wang Yi, Dong Qiang, Yu Jin-Tai
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.
Ann Transl Med. 2021 Aug;9(15):1222. doi: 10.21037/atm-21-344.
Socioeconomic status (SES) is considered to be associated with the prevalence of Alzheimer's disease (AD). However, the causal association remain unclear. Here, we determining whether income has a causal protective effect on the risk of developing AD using Mendelian randomization (MR).
Single-nucleotide polymorphisms (SNPs) that are strongly associated with household income levels (P<5×10) from the UK Biobank (UKB) (n=286,301) were selected as instrumental variables for this study. Confounding instruments were removed through data set browsing. Selected SNPs were then harmonized with results from an AD genome-wide meta-analysis (71,880 cases, 383,378 controls) including both case-control and proxy cases. The analysis was conducted using MR methods, and multiple sensitivity analyses were applied for testing of potential bias.
After confounding instrument removal and clumping, 9 SNPs associated with household income level identified by the UKB were left for the MR analysis. Our results demonstrated that higher household income level was causally related with a lower risk of AD (odds ratio 0.78, 95% confidence interval: 0.69-0.89; P<0.001). Multiple sensitivity analyses suggested no obvious evidence for heterogeneity or pleiotropy of the results.
Under MR assumptions, our results suggest robust evidence of a causal association between household income and AD risk, which may provide potential prevention strategies for this devastating disease.
社会经济地位(SES)被认为与阿尔茨海默病(AD)的患病率有关。然而,因果关系仍不明确。在此,我们使用孟德尔随机化(MR)方法确定收入对患AD风险是否具有因果保护作用。
从英国生物银行(UKB)(n = 286,301)中选择与家庭收入水平密切相关(P<5×10)的单核苷酸多态性(SNP)作为本研究的工具变量。通过数据集浏览去除混杂工具变量。然后将选定的SNP与AD全基因组荟萃分析(71,880例病例,383,378例对照)的结果进行整合,该分析包括病例对照和替代病例。使用MR方法进行分析,并应用多种敏感性分析来测试潜在偏倚。
在去除混杂工具变量并进行聚类后,保留了UKB鉴定的9个与家庭收入水平相关的SNP用于MR分析。我们的结果表明,较高的家庭收入水平与较低的AD风险存在因果关系(优势比0.78,95%置信区间:0.69 - 0.89;P<0.001)。多种敏感性分析表明,没有明显证据表明结果存在异质性或多效性。
在MR假设下,我们的结果表明家庭收入与AD风险之间存在因果关联的有力证据,这可能为这种毁灭性疾病提供潜在的预防策略。