Scientists have identified a gene that doubles the risks of respiratory failure and death from Covid and could explain why people of south Asian heritage are more vulnerable to the disease.
The gene, which changes the way the lungs respond to infection, is the most important genetic risk factor identified so far and is carried by roughly 60% of people with south Asian backgrounds, compared with 15% of those with white European backgrounds. The finding could partly explain the excess deaths seen in some communities in the UK and the impact of Covid-19 in the Indian subcontinent.
Prof James Davies, a geneticist at Oxford University’s Radcliffe Department of Medicine and a senior author of the paper, said: “The genetic factor we have found explains why some people get very seriously ill after coronavirus infection … There’s a single gene that confers quite a significant risk to people of south Asian background.”
However, other scientists cautioned that the findings needed further confirmation and that genetic explanations should not overshadow other potentially more significant socioeconomic risk factors faced by ethnic minorities, including workplace exposure and unequal access to healthcare.
The study builds on previous work that identified a large chunk of DNA that appeared to influence how severely ill people become from Covid, based on genetic sequencing of tens of thousands of hospital patients in the UK and other countries. The latest study homed in on a single gene called LZTHL1, which was revealed to double the risk of respiratory failure and death.
The gene, which was previously unstudied, was found to act as a switch to turn on a crucial defence mechanism that prevents the Covid-19 virus from entering epithelial cells that line the lung. With the high-risk version of the gene, this response was blunted, meaning the virus would continue entering, infecting and damaging cells in the lung for a longer time period after exposure.
“Although we cannot change our genetics, our results show that the people with the higher-risk gene are likely to particularly benefit from vaccination,” said Davies. “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.”
Davies said the findings also pointed to the possibility of new treatments targeting the lung cells’ response. Most current treatments work by changing the way the immune system responds to the virus.
The findings could offer some explanation for why south Asian populations have been worst affected in the pandemic. In England’s second wave, ONS data showed a risk of death three to four times higher for people of Bangladeshi backgrounds, 2.5 to three times higher for those of Pakistani backgrounds and 1.5 to two times higher for Indian backgrounds compared with the general population.
Unlike the excess risk seen in black populations in the first wave, in south Asian groups there remained a significant unexplained risk once socio-economic factors were taken into account. “[Genetic factors] would account for a large proportion of that,” said Davies.
Raghib Ali, of the University of Cambridge and an independent expert adviser on Covid-19 and ethnicity to the Race Disparity Unit in the Cabinet Office, said: “This is an important study which contributes to our ongoing efforts to understand the causes of the higher death rates from Covid in some ethnic groups and specifically as to why their outcomes or survival from Covid are worse after infection.”
However, others urged caution. Nazrul Islam, of Oxford University’s Nuffield Department of Population Health, pointed out that some ethnicities are not well represented in the large genetic databases used to determine the prevalence of particular genes such as LZTHL1.
“It provides an easy gateway for policymakers to say ‘it’s genetic, we can’t do anything’,” he said. “We have to be very careful in analysing the data, questioning it repeatedly, and how we disseminate the findings. It has profound social issues.”
The study is published in the journal Nature Genetics.