Dementia Gene Raises Risk of Severe COVID-19; UConn Health Researcher Analyzes Potential Groundbreaking Data

Having a specific gene, which previous genetic studies have found to be linked to dementia, doubles the risk of developing severe COVID-19, according to a newly published large-scale study with data analysis led by a University of Connecticut researcher. 

A research team at the University of Exeter Medical School and the UConn School of Medicine analyzed data from the UK Biobank, and found a high risk of severe COVID-19 infection among participants of European ancestry who carry two faulty copies of the APOE gene.  One in 36 people of European ancestry have two faulty copies of this gene, and this is known to increase risks of Alzheimer’s disease up to 14-fold and also increases the risk of heart disease.

“This is an exciting result because we might now be able to pinpoint how this faulty gene causes vulnerability to COVID-19. This could lead to new ideas for treatments,” co-author Chia-Ling Kuo, assistant professor in the Department of Public Health Sciences at the UConn School of Medicine told UConn Today. 

The research team found that carrying these gene mutations doubles the risks of COVID-19 – even in people who had not developed these diseases.  Kuo told CT by the Numbers that while it is not surprising that two copies of e4 (e4e4) was associated with increased risk of covid-19 severity, “it is surprising that the association is independent of dementia, also found in people without dementia.”  Kuo is a researcher at UConn’s Connecticut Convergence Institute for Translation in Regenerative Engineering and the UConn Center on Aging. The study found that presence of the faulty genes “increases risks of severe COVID-19 infection, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes.”

The team has previously found that people with dementia are three times more likely to get severe COVID-19. Part of the increased risk effect may have been exposure to the high prevalence of the virus in nursing homes. However, the new study, published on May 26 in the Journal of Gerontology: Medical Sciences, indicates that the genetic component may also be at play, UConn Today reported.

The team found that people with the APOE e4e4 genotype were at double the risk of developing severe COVID-19, compared to those with the common e3e3 form of the APOE gene. The team used data from the UK Biobank study, which collects health and genetic data on 500,000 people.

Kuo describes her research interests as focusing on genetic epidemiology in aging and applied biostatistics in medical and dental sciences.  Her Ph.D. from the University of Pittsburgh is in biostatistics and statistical genetics. Her postdoctoral training was at the National Institute of Environmental Health Sciences (NIEHS).

During her postdoctoral training at NIEHS, Kuo’s research has been focused on design and analysis of large-scale genetic association studies, including collaboration with experts in aging and independent research. She has a track record of publications and funding using large cohorts including UK Biobank and Health Retirement Study to examine genetics and epidemiology of aging, and has presented papers and talks to leading scientific organizations in the U.S. and internationally.

Of the study findings, Kuo points out that “It’s also important because it shows again that increasing disease risks that appear inevitable with aging might actually be due to specific biological differences, which could help us understand why some people stay active to age 100 and beyond, while others become disabled and die in their sixties.”

Professor David Melzer, Epidemiology and Public Health Group, University of Exeter Medical School,  who led the team, told UConn Today: “Several studies have now shown that people with dementia are at high risk of developing severe COVID-19. This study suggests that this high risk may not simply be due to the effects of dementia, advancing age or frailty, or exposure to the virus in care homes.  The effect could be partly due to this underlying genetic change, which puts them at risk for both COVID-19 and dementia.”

Looking ahead, Kuo told CT by the Numbers that the team is encouraging researchers to join the effort to better understand the “underlying mechanism between apoe e4 and covid-19 severity.”  Extending their work in data science, they’d be interested in learning if these findings “can be replicated in other populations and if the genetic effect is moderated by other factors, e.g., medications.”