A ‘Dementia Gene’ Doubles Your Risk Of Severe COVID-19
by JV Chamary
People aren't equally susceptible to coronavirus disease.
We know relatively little about which factors influence the severity of symptoms you would experience if infected by the SARS-CoV-2 virus. The elderly are especially vulnerable, for example, but the reasons why are a lot more complex than a weaker immune system.
Medical researchers have now identified one factor that influences your risk of severe disease: a variant of the gene 'APOE', which is associated with dementia. You normally inherit two copies of this 'dementia gene' (one from each parent), which comes in variants that include e3 and e4.
Among individuals of European ancestry, the most common APOE genotype is two copies of the e3 variant, e3/e3, which isn't linked to dementia. But in around 1 in 36 'Europeans', both copies are e4 (you have the letter 'C' instead of 'T' in your DNA) and the gene produces a faulty APOE protein. This variant is a common genetic factor associated with late-onset Alzheimer's disease.
According to the new study, people who carry APOE e4/e4 have twice the risk of developing severe COVID-19 (when compared to those with e3/e3), as discovered after scanning the UK Biobank, a database containing DNA sequences from half a million volunteers.
I understand more than most about APOE after having my whole genome sequenced. Reading every letter in my DNA revealed that I have one copy of each APOE variant (my immediate ancestors originated from Asia via Africa).
Note that if, like me, you carry the e3/e4 combination of APOE variants, it's unlikely you'll be at higher risk of severe COVID-19 because a working gene can often make enough protein to compensate for the other, faulty variant. By analogy, missing one functional gene isn't like a car you can't drive because it's missing a wheel, but like a broken headlamp — the working light will still let you see the road in the dark.
The new analysis was published in the Journal of Gerontology: Medical Sciences and carried out by researchers at the University of Exeter in the UK and the University of Connecticut in the US. The two teams previously showed that those with dementia are three times more likely to suffer from severe COVID-19. That result could potentially be explained by older people having an increased chance of exposure to the virus in care homes, however. The new research suggests a genetic factor is also involved.
Of the 382,188 participants in the BioBank with European ancestors, 9022 (2.4%) carry the faulty e4/e4 genotype. And of the 721 individuals who tested positive for coronavirus, 37 (5.1%) also have those genetic variants of ApoE.
APOE stands for 'apolipoprotein E' and, as the lipid part of its name implies, the gene produces a protein that enables our bodies to transport cholesterol and other kinds of fat through the bloodstream — which is why variants of this so-called 'dementia gene' are also associated with cardiovascular conditions. This highlights how faulty APOE genes can have knock-on effects beyond the blood and brain — including the body's response to COVID-19.
The study was led by epidemiologist David Melzer, who emphasised that the greater vulnerability to severe disease isn't just down to ageing — genetic predisposition also plays a part. "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."