One human gene doubles the risk of dying from COVID-19

OXFORD, United Kingdom — A single gene may be responsible for doubling the risk of death from COVID-19 among certain patients, a new study warns. Researchers from Oxford University say this gene variant keeps the cells in the lungs from properly responding to the virus. Concerningly, 60 percent of people of South Asian ancestry carry this high-risk gene.

The team notes this helps to explain the higher death rates in some communities within the United Kingdom, as well as the pandemic’s impact on the Indian subcontinent. Although previous studies have identified portions of human DNA which increase the risk of dying from COVID-19, scientists did not know how this genetic signal worked or which genetic changes trigger this potentially fatal reaction to coronavirus.

“The reason this has proved so difficult to work out, is that the previously identified genetic signal affects the ‘dark matter’ of the genome. We found that the increased risk is not because of a difference in gene coding for a protein, but because of a difference in the DNA that makes a switch to turn a gene on. It’s much harder to detect the gene which is affected by this kind of indirect switch effect,” study co-lead and professor of gene regulation Jim Hughes says in a university release.

Carrying LZTFL1 can lead to death from COVID

The team used brand new technology to help them examine COVID infections at a genetic level. Specifically, they trained an artificial intelligence algorithm to scan through huge amounts of genetic data from cells throughout the human body. That review showed that the genetical signal is more likely to affect cells in the lungs.

From there, researchers zoomed in to look at this DNA, examining the way billions of DNA fragments fold up to fit inside a single cell. This helped them pinpoint the exact gene involved in creating a greater risk of severe COVID infection.

“Surprisingly, as several other genes were suspected, the data showed that a relatively unstudied gene called LZTFL1 causes the effect,” Dr. Damien Downes explains.

Study authors believe LZTFL1 prevents cells lining the airways and the lungs from properly reacting to the virus. However, this gene variant doesn’t appear to impact the immune system, which means people who carry this version of the gene should still respond normally to receiving the COVID-19 vaccine.

“The genetic factor we have found explains why some people get very seriously ill after coronavirus infection. It shows that the way in which the lung responds to the infection is critical. This is important because most treatments have focused on changing the way in which the immune system reacts to the virus,” says study co-lead Professor James Davies, a National Health Service consultant in intensive care medicine and associate professor of genomics at Oxford.

Who carries this high-risk gene?

As for who carries this gene, the study finds a majority of people of South Asian ancestry appear to carry LZTFL1. Conversely, just 15 percent of those with European ancestry carry the gene.

Interestingly, just two percent of people with Afro-Caribbean ancestry carry this gene variant, despite studies noting higher COVID death rates among Black and minority communities. The team believes, in these cases, social factors likely play a key role in people suffering a life-threatening case of COVID-19.

“The higher risk DNA code is found more commonly in some black and minority ethnic communities but not in others. Socioeconomic factors are also likely to be important in explaining why some communities have been particularly badly affected by the COVID-19 pandemic,” Prof. Davies concludes.

“Although we cannot change our genetics, our results show that the people with the higher risk gene are likely to particularly benefit from vaccination. Since the genetic signal affects the lung rather than the immune system it means that the increased risk should be cancelled out by the vaccine.”

The findings appear in the journal Nature Genetics.

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