Ancestry study explores COVID-19 genetic risks

As researchers around the globe pursue tests, treatments and vaccines for the COVID-19 virus, a significant portion of scientific brain power is being expended to determine which groups of people are most susceptible to infection, what positive patients are most likely to develop severe symptoms and other possible risks.

Scientists at Ancestry recently completed a comprehensive analysis of self-reported survey data of more than 563,000 US adults, including more than 4,700 COVID-positive people, in an attempt to determine which individuals might be most at risk. Ancestry’s chief scientific officer Dr. Cathy Ball (CB) recently talked with Outsourcing-Pharma (OSP) about the study and what it might reveal to researchers working on potential COVID-19 therapies.

OSP: Could you please provide an overview of some of the research projects Ancestry has contributed to around human health?​

CB: Ancestry routinely facilitates studies using our Personal Discoveries Project. Given the scale of this pandemic, we felt it imperative to do our part to support the global research community in the quest to defeat COVID-19 and have been proactively engaging our members who’ve consented to participate in research.

OSP: Could you please share how this particular COVID-19 study was conceived?​

CB: Like everyone else, we watched the initial months of the pandemic with deep concern.  The observation that the disease severity varied from person to person made us wonder if genetics might be involved.

As part of our commitment to health, Ancestry is making research data from the study available at no cost to qualified researchers in organizations. Nearly 800,000 members of Ancestry’s DNA network have consented to participate in this study.

OSP: Please provide a little more detail about how the study put together the survey, collected responses, then married with information from the AncestryDNA database for analysis.​

CB: As part of the study, we are collecting feedback related to a person’s exposure and response to exposure, behavior and co-morbidities related to COVID-19. Survey responses from individuals who consent to participate are combined with their DNA data, aggregated with other participant data, and shared with qualified researchers working to accelerate the development of preventative or therapeutic treatments for COVID-19.

Before these data are shared, they are de-identified (stripped of direct and indirect identifiers like name, place of birth, and so on) and aggregated with other data to protect the privacy of participants.

OSP: Could you please tell us about some of the key findings, and any conclusions you might have been able to come up with as a result?​

CB: With this study we are already learning new information about both susceptibility (why some people are more likely to be infected) and severity (why some people suffer severely and others only mildly) of the disease. 

Our researchers identified a DNA region which may be associated with COVID-19 susceptibility near the IVNS1ABP gene. This association, only present in males, could help explain why the novel coronavirus that causes COVID-19 seems to take a greater toll on men than women.

Exploring the self-reported, de-identified survey responses provided by Ancestry customers from all 50 states in both urban and rural areas, we are also learning more about personal choices around the use of masks and physical distancing. We hope these insights will contribute to the body of knowledge around preventive measures and will be validated by other researchers with clinical information.

We observed that those infected with severe COVID-19, determined by being hospitalized or becoming a critical case, were less likely to report having worn a mask inside within seven days prior to their illness onset, compared to those who weren't hospitalized. This finding, based on an investigation in over 3,000 people with symptomatic COVID-19, holds true even after accounting for differences in age, biological sex, and comorbidities.

This trend, that preventive measures are associated with a less severe outcome, is also observed for those who report having worn masks outside and practiced physical distancing.

OSP: Please tell us about the three novel loci. What are the potential implications of these loci in diagnosing/predicting COVID-19 infections, predicting possible severity, developing therapies, etc.​

CB: Results from an early analysis of the self-reported data with genetic data identified three novel loci with known roles in viral replication or immunity in addition to replicating two loci identified in previous studies from other groups. The strongest association was found near IVNS1ABP, a gene involved in influenza replication, and was, interestingly, found to be only associated in males; this suggests possible differences between how men and women respond to COVID-19.

These data are preliminary and require validation from an independent dataset.  They were shared early to help accelerate the pace of research.  These summary results have been shared with the international COVID-19 Host Genetics Initiative to continue the examination and validation of results.

OSP: Your summary posits that this story contains evidence that host genetic variation contributes to C19 outcomes—can you share any more specifics about what genetic variations might be at play?​

CB: We know relatively little about how the novel coronavirus affects an individual. Whereas traditional clinical tests might be able to give some indication of how sick a person is and what treatments might be most effective in helping a patient’s condition, understanding the role of specific genetic variation might better indicate why certain people become more sick than others and have different clinical outcomes.

There have been many studies implicating various genetic loci correlated with COVID-19, but there are just a handful that are replicated consistently. These include two signals on chromosome 3 near the LZTFL1 gene, one associated with susceptibility and one associated with severity, the ABO locus on chromosome 9 (associated with blood type), and a signal near the IFNAR2 gene on chromosome 21 associated with severity.

We replicate all of these signals in our data across multiple phenotypes for both susceptibility and severity, adding to the evidence that these specific genetic variants may be influencing one's susceptibility to or severity of COVID-19.

In addition to replicating known signals, we have identified a novel locus on chromosome 1 observed in men only, which if replicated, could potentially explain a portion of the increased risk observed in males.

OSP: How does this study underscore the importance of self-reported data in tackling a health crisis?​

CB: By collecting over 500,000 responses in under two months, our COVID-19 Research Study has demonstrated that self-reported data can be collected at scale in a short amount of time.  These data are consistent with national trends, as compared to those reported by the CDC during a similar period of time.

These data have been used to power insights about outcomes of the general population, understand the impact of behaviors such as wearing PPE to protect ourselves from disease severity, identify risks factors associated with susceptibility and severity of COVID-19, and host genetics. 

When speed and scale of data collection is required to gain knowledge about a health crisis, we have demonstrated in our broad range of results that self-collected data can power valuable insights.