Objective
COVID-19 might cause neuroinflammation in the brain, which could decrease neurocognitive function. We aimed to evaluate the causal associations and genetic overlap between COVID-19 and intelligence.
Methods
We performed Mendelian randomization (MR) analyses to assess potential associations between three COVID-19 outcomes and intelligence (N = 269,867). The COVID phenotypes included SARS-CoV-2 infection (N = 2,501,486), hospitalized COVID-19 (N = 1,965,329), and critical COVID-19 (N = 743,167). Genome-wide risk genes were compared between the genome-wide association study (GWAS) datasets on hospitalized COVID-19 and intelligence. In addition, functional pathways were constructed to explore molecular connections between COVID-19 and intelligence.
Results
The MR analyses indicated that genetic liabilities to SARS-CoV-2 infection (OR: 0.965, 95% CI: 0.939-0.993) and critical COVID-19 (OR: 0.989, 95% CI: 0.979-0.999) confer causal effects on intelligence. There was suggestive evidence supporting the causal effect of hospitalized COVID-19 on intelligence (OR: 0.988, 95% CI: 0.972-1.003). Hospitalized COVID-19 and intelligence share ten risk genes within two genomic loci, including MAPT and WNT3. Enrichment analysis showed that these genes are functionally connected within distinct subnetworks of 30 phenotypes linked to cognitive decline. The functional pathway revealed that COVID-19-driven pathological changes within the brain and multiple peripheral systems may lead to cognitive impairment.
Conclusions
Our study suggests that COVID-19 may exert a detrimental effect on intelligence. The tau protein and Wnt signaling may mediate the influence of COVID-19 on intelligence.