Dementia Gene Raises Risk of Severe COVID-19

Having a faulty gene linked to dementia doubles the risk of developing severe COVID-19, according to a large-scale study.

Researchers 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 (termed e4e4). 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. Now, the research team has found that carrying these gene mutations doubles the risks of COVID-19 – even in people who had not developed these diseases.

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 a genetic component may also be at play. 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.

In this analysis, 2.36% (n=9,022) of participants with European ancestries (n=382,188) had the ApoE e4e4 faulty gene, but 5.13% (n=37) of those who tested positive for COVID-19 (n=721) had this gene variant, suggesting the risk is doubled compared to e3e3 (410 per 100,000 versus 179 per 100,000).

“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,” says co-author Chia-Ling Kuo, assistant professor in the Department of Public Health Sciences at the UConn School of Medicine. She is also a researcher at UConn’s Connecticut Convergence Institute for Translation in Regenerative Engineering and the UConn Center on Aging.

Kuo adds: “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, who led the team, says: “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.”

Dr Chia-Ling Kuo, who led the data analysis and is first author on the paper, is supported in part by the US National Institute on Aging (R21AG060018).

UK Biobank is a study of 500,000 volunteers set up in 2006 for researchers to track the health of participants over time. During the period studied (16th March to 14th April 2020, in England only) tCOVID-19 testing was largely restricted to hospital in-patients with clinical signs of infection, so test positivity is a good marker of severe COVID-19.

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