Exploring the influence of genetics on COVID-19

Helix researchers to leverage user input and exome-sequencing data to understand COVID-19 risk and severity

The spread of the novel SARS-CoV-2 coronavirus has led to the unfolding COVID-19 pandemic. In addition to demonstrating a high degree of transmissibility, a significant barrier to the treatment and containment of this virus has been the variability in symptoms that results from infection—ranging from life-threatening pneumonia in some, to no observable illness in others. This spectrum of vulnerability and disease severity is likely a result of many factors, including heritable variations in a person’s DNA.

During the HIV epidemic, for example, researchers found that approximately 1% of European ancestry individuals were immune to HIV infection owing to a deletion in the host coreceptor CCR51–3. Similar research examining the influence of genetics on COVID-19 pathophysiology could help us identify those who are at a higher risk of developing COVID-19 and certain disease outcomes.

Over the next several weeks, Helix researchers will be reaching out to the hundreds of thousands of individuals who have been sequenced using the Exome+® assay with a simple survey that collects information about a person’s possible exposure to COVID-19, any symptoms (or lack thereof) that they may be experiencing, and any medications they may be taking. This information will then be paired with each respondent’s genetic data and used to identify potential patterns that reveal insights into why some people are more vulnerable to COVID-19 compared to others.

How genetics might play a role in COVID-19

In order to infect a person, viruses like the SARS-CoV-2 virus—the one responsible for COVID-19—have to find a way to enter the person’s cells and then trick those cells into producing copies of the virus (which then find more cells to infect and the cycle repeats itself).

Environmental and genetic factors can make this infection cycle easier or harder for the virus 4-6. For example, it is believed that the SARS-CoV-2 virus enters cells by interacting with the ACE2 protein which is displayed on the outer surface of certain cells. If a person has inherited variants in their DNA that change the shape of the ACE2 protein, it may prevent the SARS-CoV-2 virus from being able to enter cells—thus decreasing a person’s vulnerability to the virus.

At the moment, that scenario is speculative; it’s currently unknown if changes in the ACE2 gene affect a person’s vulnerability. However, through this survey, Helix researchers will be able to investigate this and other potential links between genetics and COVID-19. It’s expected that natural changes in a person’s DNA may alter how their body reacts to the virus, how hard it is for the virus to get a foothold in their body, and how effective certain therapeutics are in treating the virus. Helix’s researchers aim to study all of this with the hope that their findings will help other researchers identify potential healthcare strategies for identifying those who are most at risk as well as potential therapeutics for treating—and maybe even preventing—COVID-19 infection.

Why sequencing matters

The genomic data being used in this research was generated using the Exome+® assay—a panel-grade, clinical exome enhanced by the inclusion of roughly 300,000 informative non-coding regions. This assay has previously been used to uncover significant associations between rare variants and clinical phenotypes in analyses that would not have been possible using microarray technology.

Using broad and deep sequencing data is critical for this type of research. Relying only on microarray technology, which is common for many consumer-focused companies, misses all of the rare variants that change the protein-coding portions of individual genomes and make each person unique. With Exome+ data, researchers will be able to study the potential influence of both common and rare variants on COVID-19 related phenotypes, opening the door to novel breakthroughs in our understanding of this disease.

Protecting research participants’ data

Helix’s research on COVID-19 is overseen and approved by an Institutional Review Board (IRB), an objective oversight committee which is tasked with ensuring that the safety and wellbeing of research participants is protected and that privacy and ethical standards for biomedical research are met.

Helix securely stores research participants’ genetic information and does not share any individual-level data with third parties unless the participant has given Helix express consent to do so. Participants in Helix-sponsored research studies retain control over their individual-level data and can decide whether or not they want it to be used for additional research.

Those who have already been sequenced by Helix can contribute to genetics research and the fight against COVID-19 by first agreeing to participate in the Helix DNA Discovery Project and subsequently taking the COVID-19 survey. De-identified data (which is data that cannot be linked back to an individual) from consented participants will be shared with a global coalition of approved researchers. Data will be de-identified and combined with other data sets in a manner that enables researchers to make discoveries that would not have been possible from a single study, while still protecting the privacy of participants. Participating in research that is structured in this way allows participants to contribute to research efforts that may help people the world over without worrying about the privacy of their individual-level data.

References

1. Dean, M. et al. Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene. Science 273, 1856–1862 (1996).

2. Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367–377 (1996).

3. Samson, M. et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382, 722–725 (1996).

4. Kaiser, J. How sick will the coronavirus make you? The answer may be in your genes. Science (2020) doi:10.1126/science.abb9192.

5. Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565–574 (2020).

6. Wan, Y., Shang, J., Graham, R., Baric, R. S. & Li, F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J. Virol. 94, (2020).