Five gene variants found that raise virus risk
Five gene variants that raise the risk of becoming seriously ill from coronavirus have been discovered by scientists, in a breakthrough that could lead to life-saving treatments.
The discovery helps explain why some people are more susceptible to the disease and may hint at why some families and ethnic groups are disproportionately affected.
Researchers from the University of Edinburgh made the discovery by studying the DNA of 2,700 COVID-19 patients in 208 intensive-care units in the U.K.
They compared the genetic data with samples from healthy volunteers to find out what was different in the DNA of those who became seriously ill.
The team found key differences in five genes — IFNAR2, TYK2, OAS1, DPP9 and CCR2 — that are individually carried by between six and 68 per cent of the population.
The genes are involved in two processes in the body — antiviral immunity and lung inflammation — and crucially can be dialed up or down by drugs already available.
Dr. Kenneth Baillie, the project’s chief investigator at the university’s Roslin Institute, said: “We’ve known for many years that variation in susceptibility to infection is strongly genetic.
“What we’ve been trying to do is use genetics to understand the complexity of the human immune system to find levers we can pull that will change the outcome for the patient.
“Essentially we’re using genetics to predict the effect of drugs that treat them in the system.”
Since the 1980s, scientists have known that genetics play a large part in how long a person may live. Studies have shown that if a parent dies of an infection, a biological child is at nearly six times the risk of dying from the same infection but an adopted child has barely any increased risk.
Having highlighted the genes, the team could predict the effects of drugs on patients, as some genetic variants respond in a similar way to particular drugs.
For example, they showed a reduction in the activity of the TYK2 gene protects against COVID-19. A class of anti-inflammatory drugs called JAK inhibitors, already used in rheumatoid arthritis, can dampen gene activity and are likely to help patients severely ill with COVID.
They also found a boost in INFAR2 activity is also likely to create protection, as it mimics the effect of treatment with interferon — special proteins released by cells of the immune system to defend against viruses.
Experts caution that to be effective, patients might need the treatment early in disease.
Based on the findings, published in Nature, the team says clinical trials should focus on drugs that target these specific areas.
Prof. Sir Mark Caulfield, chief scientist for Genomics England and director of the NIHR Biomedical Research Centre at Barts, Queen Mary University of London, said: “This study takes the morass of biology and shines a light on very specific places, and then says, actually, there is a treatment. It’s not used for this, we didn’t have a clue it would be useful.
“In terms of a leap forward it’s a quantum leap forward.”
The GENOMICC (Genetics of Susceptibility and Mortality in Critical Care) study started in 2015 to look at genetic factors that influence outcomes in intensive care from diseases such as SARS, influenza and sepsis. It was given urgent public health research status this year to look for genes linked to the novel coronavirus.
The team is now keen to understand if the genes are linked to specific ethnic groups and want volunteers from the ethnic minorities to come forward.
Four of the gene variants are common in people of South Asian descent, and they are known to be at greater risk.
Dr. Jonathan Pear ce, COVID-19 response interim director at the Medical Research Council, which helped fund the project, said: “Identifying genes associated with severe COVID-19, including in young patients without known underlying health issues, will allow us to better target and accelerate research into new diagnostic and therapeutic approaches.