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Are some people at greater genetic risk from Covid-19? MRC Laboratory of Molecular Biology seeks DNA volunteers




An international study has been launched in Cambridge that could reveal whether a person’s genetic make-up can increase his or her risk of being severely affected by Covid-19.

Prof Julian Gough, a group leader at the MRC Laboratory of Molecular Biology, is asking those who have had a consumer DNA test carried out by the likes of 23andMe or AncestryDNA to aid the research by volunteering their data.

Companies now offer consumer DNA testing
Companies now offer consumer DNA testing

Upload your DNA file at supfam.mrc-lmb.cam.ac.uk/SUPERFAMILY/23andMe/ and wait 24 hours for a supercomputer to process it, then a questionnaire tailored to you will be provided, followed by some predictions relating to unusual or interesting parts of your DNA.

The data, which will be used anonymously, will aid the LMB in exploring whether DNA genotype can be used to predict Covid-19 risk factors.

Prof Gough told the Cambridge Independent: “It seems clear that the two main influences on coronavirus infection outcome are age and pre-existing conditions. So genetic risk factors are not the most important. However, it is likely that there are some genetic risk factors – it is still worth doing.

“For the very small percentage of people who this probably affects, knowledge of – and ultimately a test for – these factors could be life-saving. Even a small percentage can translate to a massive number of people.”

A number of human genetics studies already exist around the world that attempt to stratify the population – that is, separate them into risk groups for the coronavirus. Among these is one announced by 23andMe and academic projects such as the Harvard Personal Genome Project, and the Host Genetics Initiative at covid19hg.org.

But Prof Gough explains: “Our academic research at the MRC Laboratory of Molecular Biology uses a predictive technology that is completely different and complementary to the traditional human genetics approaches employed by all other initiatives.

“Whereas others leverage statistical correlation, ours relies on causal molecular information. It is because they are different and complementary that it is important both must be done.

“If either one or both approaches finds a statistically significant causal genetic risk factor, then it could enable the development of a test. The test could, for example, identify people who have a severe risk of death from coronavirus infection despite a young age and lack of pre-existing conditions.”

Prof Julian Gough, of the MRC Laboratory of Molecular Biology. Picture: MRC LMB (34734136)
Prof Julian Gough, of the MRC Laboratory of Molecular Biology. Picture: MRC LMB (34734136)

Consumer DNA tests, which typically use a saliva kit through the post, have become increasingly popular, with millions conducted around the world.

The LMB already has more than 800 participants in its study, which could provide information of use to others.

“If a risk factor is discovered by us, or anyone else, in a variant included in consumer genotyping arrays, then anyone who has done one of these tests will be able to look up their risk without additional testing,” explains Prof Gough.

“The technology used in this study has been eight years in development and in addition to coronavirus risk factors includes the assessment of over 6,000 other phenotypes.

“By analysing the genome we are able to personalise each person’s questionnaire to ask them a small number of questions, from the 6,000, which are tailored to their genome. It is truly personalised.”

Studies have already been exploring whether variants in an individual’s ACE2 gene could have an impact on their susceptibility to the SARS-CoV-2 virus that causes Covid-19. The virus appears to be optimised to bind with this receptor, and ACE2 plays a key role in enabling the virus to enter into the cell.

However, the LMB study has the potential to identify genes that we did not know had any impact on Covid-19 infection risk.

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19). Picture: Alissa Eckert, MS; Dan Higgins, MAMS; CDC (34734142)
This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus, named Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019. The illness caused by this virus has been named coronavirus disease 2019 (COVID-19). Picture: Alissa Eckert, MS; Dan Higgins, MAMS; CDC (34734142)

Could it find evidence, perhaps, of genetic variants affecting our propensity to a cytokine storm? In this process, which affects the worst-hit Covid-19 patients, the immune system goes haywire, activating large numbers of white blood cells and releasing inflammatory cytokines.

It is also possible the study could uncover risk factors for different ethnic groups. People of black, Asian and minority ethnic (BAME) backgrounds have been disproportionately affected by the novel coronavirus.

While societal issues are involved, data from the Office for National Statistics adjusted for socio-demographic characteristics shows there are further unexplained factors, which could be genetic.

“It is possible we will see differences between ethnic groups,” said Prof Gough.

“Our priority and the thrust of our approach is to see if we can uncover causal variation in genes based on molecular biology.

“Should we discover anything, the first thing we will ask is how plausible this is and whether we can do anything to validate it independently.

“The second thing we will do is to look at haplotype distribution of any variation – this will tell us if indeed our particular discovery is specific to BAME people.

“The government data points strongly towards a genetic link, but we cannot say in advance whether something we discover will be part of that link or part of something else.”

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