COVID-19 与阿尔茨海默病风险和进展的关联：基于 260 万受试者的非重叠两样本孟德尔随机分析。

Association of COVID-19 with Risk and Progression of Alzheimer's Disease: Non-Overlapping Two-Sample Mendelian Randomization Analysis of 2.6 Million Subjects.

机构信息

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.

出版信息

J Alzheimers Dis. 2023;96(4):1711-1720. doi: 10.3233/JAD-230632.

DOI:10.3233/JAD-230632

PMID:38007657

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11037518/

Abstract

BACKGROUND

Epidemiological studies showed that COVID-19 increases risk of Alzheimer's disease (AD). However, it remains unknown if there is a potential genetic predispositional effect.

OBJECTIVE

To examine potential effects of genetic susceptibility of COVID-19 on the risk and progression of AD, we performed a non-overlapping 2-sample Mendelian randomization (MR) study using summary statistics from genome-wide association studies (GWAS).

METHODS

Two-sample Mendelian randomization (MR) analysis of over 2.6 million subjects was used to examine whether genetic susceptibility of COVID-19 is not associated with the risk of AD, cortical amyloid burden, hippocampal volume, or AD progression score. Additionally, a validation analysis was performed on a combined sample size of 536,190 participants.

RESULTS

We show that the AD risk was not associated with genetic susceptibility of COVID-19 risk (OR = 0.98, 95% CI 0.81-1.19) and COVID-19 severity (COVID-19 hospitalization: OR = 0.98, 95% CI 0.9-1.07, and critical COVID-19: OR = 0.98, 95% CI 0.92-1.03). Genetic predisposition to COVID-19 is not associated with AD progression as measured by hippocampal volume, cortical amyloid beta load, and AD progression score. These findings were replicated in a set of 536,190 participants. Consistent results were obtained across models based on different GWAS summary statistics, MR estimators and COVID-19 definitions.

CONCLUSIONS

Our findings indicated that the genetic susceptibility of COVID-19 is not associated with the risk and progression of AD.

摘要

背景

流行病学研究表明，COVID-19 会增加患阿尔茨海默病（AD）的风险。然而，目前尚不清楚是否存在潜在的遗传易感性。

目的

为了研究 COVID-19 的遗传易感性对 AD 的风险和进展的潜在影响，我们使用来自全基因组关联研究（GWAS）的汇总统计数据进行了非重叠的两样本 Mendelian 随机化（MR）研究。

方法

使用超过 260 万受试者的两样本 Mendelian 随机化（MR）分析，研究 COVID-19 的遗传易感性是否与 AD 的风险、皮质淀粉样蛋白负担、海马体积或 AD 进展评分无关。此外，还对一个包含 536190 名参与者的合并样本进行了验证分析。

结果

我们表明，AD 的风险与 COVID-19 风险的遗传易感性（OR=0.98，95%CI 0.81-1.19）和 COVID-19 的严重程度（COVID-19 住院治疗：OR=0.98，95%CI 0.9-1.07，和严重 COVID-19：OR=0.98，95%CI 0.92-1.03）无关。COVID-19 的遗传易感性与海马体积、皮质淀粉样蛋白β负荷和 AD 进展评分所衡量的 AD 进展无关。这些发现在一个包含 536190 名参与者的样本中得到了复制。基于不同的 GWAS 汇总统计数据、MR 估计量和 COVID-19 定义的模型，都得到了一致的结果。