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. 2023 Jan;95(1):e28107.
doi: 10.1002/jmv.28107. Epub 2022 Sep 7.

Causal effect of COVID-19 on Alzheimer's disease: A Mendelian randomization study

Ancha Baranova  1   2 , Hongbao Cao  1 , Fuquan Zhang  3   4
Affiliations

Causal effect of COVID-19 on Alzheimer's disease: A Mendelian randomization study

Ancha Baranova et al. J Med Virol. 2023 Jan.

Abstract

It was reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause brain size reduction and cognitive decline. Whether COVID-19 may contribute to the development of Alzheimer's disease (AD) is not known. We conducted genetic correlation and Mendelian randomization (MR) analyses to assess genetic relationships and potential causal associations between AD and three COVID-19 outcomes (SARS-CoV-2 infection, COVID-19 hospitalization, and critical COVID-19) by utilizing genome-wide association study datasets on these traits. A map of COVID-19-driven molecular pathways was constructed to investigate potential mechanisms underlying the COVID-19 and AD connection. Genetic correlation analyses indicated that AD had a significant positive genetic correlation with hospitalized COVID-19 (rg = 0.271). The MR analysis from the inverse-variance-weighted model showed that genetic liabilities to hospitalized COVID-19 (odds ratio: 1.02, 95% confidence interval: 1.01-1.03) and critical COVID-19 (1.01, 1.00-1.02) were associated with an increased risk for AD. However, no causal effect of genetic liability to SARS-CoV-2 infection on AD was detected (1.03, 0.97-1.09). A total of 60 functionally interconnected genes were reported to mediate the COVID-19-AD connection, which showed functional enrichment in immunity-related pathways and tissue enrichment in the lung and brain. Our study suggests that severe COVID-19 may contribute to the development of AD, while suffering a mild case of COVID-19 may not increase the risk for AD. The influence of COVID-19 on AD may be mediated by immunity-related pathways acting predominantly in the lung and brain.

Keywords: Alzheimer's disease; COVID-19; GWAS; Mendelian randomization.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Tissue expression enrichment analyses. (A) Tissue‐specific expression analysis for hospitalized COVID‐19. (B) Tissue‐specific expression analysis for AD. (C) Gene‐based tissue enrichment analysis of the shared genome‐wide risk genes between COVID and AD. (D) Gene‐based tissue enrichment analysis of the 60 genes connecting COVID‐19 and AD. Significantly enriched differentially expressed gene (DEG) sets (p Bonferroni < 0.05) are highlighted in red. AD, Alzheimer's disease.
FIGURE 2
FIGURE 2
A map of molecular pathways connecting COVID‐19 and Alzheimer's disease (AD). Quantitative genetic changes driven by COVID‐19 exert more negative (highlighted in red) than positive (highlighted in green) effects on AD.
FIGURE 3
FIGURE 3
Protein–protein interactions among the risk genes shared between COVOD‐19 and AD. Line sizes are proportional to the combined scores of the interactions. AD, Alzheimer's disease.
See this image and copyright information in PMC

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