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

• Published in: Journal of Alzheimer's disease Vol. 96; no. 4; p. 1711
• Main Authors: Ding, Pingjian, Gurney, Mark, Perry, George, Xu, Rong
• Format: Journal Article
• Language: English
• Published: United States 01.01.2023
• Subjects: Alzheimer Disease - epidemiology; Alzheimer Disease - genetics; Amyloid beta-Peptides; COVID-19 - genetics; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide - genetics; COVID-19; cortical amyloid beta load; Alzheimer’s disease; 2-sample Mendelian randomization analysis; Alzheimer’s disease progression score; hippocampal volume
• DOI: 10.3233/JAD-230632

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