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

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.