South Asian descent gene linked to higher Covid risk: UK study

Researchers in the United Kingdom have reported that three out of five persons of South Asian ancestry carry a gene that is associated with a doubling of the risk of respiratory failure from severe Covid-19.

The study by researchers at the University of Oxford said that the high-risk version of the gene, ‘leucine zipper transcription factor like 1’, or LZTFL1, “probably” prevents the cells lining the airways and lungs “from responding to the virus properly”. The researchers also said that the genetic signal doubled the risk of dying from Covid-19 in adults under the age of 65 years.

“But importantly, it doesn’t affect the immune system, so the researchers expect people carrying this version of the gene to respond normally to vaccines,” Oxford said in a release on the findings of the study published on Thursday.

“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 release quoted study co-lead James Davies, associate professor of genomics at Oxford’s Radcliffe Department of Medicine.

The study published in Nature Genetics (‘Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus’: Hughes et al) is a genome-wide association study (GWAS) aimed at identifying candidate genes that predispose to severe Covid-19 that can cause multiple organ failure through cytokine release, etc.

The key finding of the GWAS was that 60 per cent with South Asian ancestry carry the high-risk genetic signal, compared to 15 per cent of those with European ancestry. This, the release said, “partly explains the excess deaths seen in some UK communities, and the impact of COVID-19 in the Indian subcontinent”.

The study also found that only 2 per cent of people with Afro-Caribbean ancestry carried the higher risk genetic signal, “meaning that this genetic factor does not completely explain the higher death rates reported for black and minority ethnic communities”.

Davies underlined that “socioeconomic factors are also likely to be important in explaining why some communities have been particularly badly affected by the COVID-19 pandemic”.

“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 focussed on changing the way in which the immune system reacts to the virus,” he said.

Study co-lead Jim Hughes, a professor of gene regulation, was quoted as saying: “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.”

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