The SARS-CoV-2 crisis is affecting virtually the entire planet, but it is not affecting everyone in the same way. Some people never show symptoms they recognize, some people make swift recoveries, and others suffer debilitating symptoms that put their lives in jeopardy or leave them worse off even after they recover. It is clear that genetic differences affect the progress of any given SARS-CoV-2 infection, and research into which differences matter and what they do has reached paramount importance. This is where large-scale genomics projects such as the UK Biobank study come in.
The UK Biobank project is a cohort study based on expansive data collected from approximately 500,000 subjects aged 40-69 from across the United Kingdom. Data collected from each subject includes lifestyle indicators, biomarkers from blood and urine, imaging of the body and brain, and the contents of health records, creating a detailed data set of health information. With the connection to health data, the UK Biobank gained access to longitudinal information about each subject long after the initial data was collected, creating an enormous dataset encompassing a vast range of time for a huge number of subjects. To connect this to genomic data, the UK Biobank project performed genotyping using the Applied Biosystems UK BiLEVE Axiom array on an initial 50,000 participant samples and using the Applied Biosystems UK Biobank Axiom array on the remaining 450,000 participant samples. The two arrays are extremely similar (with over 95% common content) and both recognize ~850,000 variants. With both genotype data and detailed, longitudinal health data, the UK Biobank project enables research into the genetic components of a wide variety of health conditions, including risk factors for infectious diseases. Two recent studies take advantage of the scale of the UK Biobank dataset to investigate risk factors potentially connected to SARS-CoV-2, helping direct future research.
Noticing the longstanding connection between hypertension, reduced pulmonary function, and pneumonia observed in small studies, Zekavat et al. used the UK Biobank dataset to study the epidemiological relationship between them in a much larger population. Their analyses suggest that this relationship does indeed hold, suggesting that targeting hypertension may serve to reduce incidence of pneumonia on a large scale. Just as importantly, this study suggests that hypertension, an easily measured condition, can be a proxy for measures of compromised pulmonary function, helping to potentially identify those at risk of pneumonia from respiratory infections before they actually develop pneumonia. With SARS-CoV-2 infection causing pneumonia as one of its more dangerous symptoms and given that hypertension has several known and well-characterized genomic risk factors, this provides a path toward using genomics to help predict pneumonia risk in the future. In turn, with pneumonia being a major and serious symptom of SARS-CoV-2 infection, this study provides evidence that blood pressure monitoring may potentially help identify people at risk for adverse outcomes from SARS-CoV-2 and other respiratory infections, even if they do not currently have compromised lung function. Further research is needed to confirm how relevant to SARS-CoV-2 specifically these findings are, but in the meantime, they suggest that genes related to hypertension and reduced pulmonary function may help explain why someone with no underlying health conditions can have worse health outcomes after SARS-CoV-2 infection.
In a separate study, Kachuri et al. found a different use for the UK Biobank dataset. This team examined genes related to viral infection response, hoping to find patterns that could explain different levels and kinds of antibodies observed in those infected with SARS-CoV-2. Thanks to UK Biobank’s use of Axiom arrays, they had the data they needed to analyze a very large number of genes. Specifically, they conducted integrative genome-wide and transcriptome-wide analyses of antibody response to 28 viral antigens for 16 viruses as well as SARS-CoV-2 itself, seeking to evaluate the relationship between host genetics and antibody response. Any genes or alleles they discovered can offer insight into how humans achieve immunity to SARS-CoV-2 after infection or avoid infection altogether and, with additional research, may provide direction toward vaccines, inoculations, and other potential treatments in the future.
In their preprint publication, Kachuri et al. confirm that human leukocyte antigen (HLA) class II and III genes are deeply involved in regulating immune response to a variety of viral antigens. Several specific HLA alleles involved in immune responses to common viral infections are also associated with SARS-CoV-2 infection. Most excitingly, they uncovered novel genetic determinants of viral antibody response, including BKV, MCV, and HHV7. This research provides a launchpad for further inquiries into what may make someone more or less susceptible to SARS-CoV-2 and how to potentially protect the population from this emergent threat, informing both public health and medical research.
Large, integrated datasets such as that from the UK Biobank project are critical for this kind of research. With many kinds of data linked together, they provide valuable research material for investigating the links between a wide variety of biological parameters, offering a more complete picture of living organisms and systems than smaller datasets could ever provide. The UK Biobank dataset’s longitudinal component in particular enables research at scales difficult to imagine any other way. By combining genomic and other kinds of data into a single body and making it widely available, the UK Biobank and other datasets like it enable important research efforts like these.
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Read the references
- Bycroft C. (2018) The UK Biobank resource with deep phenotyping and genomic data. Nature (DOI: 10.1038/s41586-018-0579-z).
- Zekavat SM et al. (2020) Influence of blood pressure on pneumonia risk: Epidemiological association and Mendelian randomisation in the UK Biobank. Preprint at medRxiv (DOI: 10.1101/2020.04.19.20071936).
- Kachuri, L et al. (2020) The landscape of host genetic factors involved in infection to common viruses and SARS-CoV-2. Preprint at medRxiv (DOI: 10.1101/2020.05.01.20088054)
- Morella, R (2020) UK Biobank: DNA to unlock coronavirus secrets [Online]. Available at: https://www.bbc.com/news/health-52243605 (Accessed 11 May 2020).
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