Association of COVID-19 with Risk and Progression of Alzheimer’s Disease: Non-Overlapping Two-Sample Mendelian Randomization Analysis of 2.6 Million Subjects
Affiliations: [a] Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| [b] Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA
| [c] Department of Neuroscience, Development and Regenerative Biology, College of Sciences, The University of Texas at San Antonio, San Antonio, TX, USA
Correspondence:
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Correspondence to: Rong Xu, Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland 44106, USA. Tel.: +1 216 368 0023; E-mail: rxx@case.edu.
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.
