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Constructing the human genetic architecture of COVID-19

In an early manuscript, the COVID-19 Host Genetics Initiative has reported 13 human genomic loci that are significantly associated with COVID-19 susceptibility and severity.

Emerging SARS-CoV-2 strains have highlighted an urgent need for efficacious intervention strategies against COVID-19. Although efficacious vaccines have been rolled out, there are still a lack of effective treatments.

A diverse range of factors contribute to the vulnerability and response to SARS-CoV-2 infection. Among them is individual genetic makeup. Understanding the genetic determinants of disease susceptibility and severity could provide novel new targets for therapeutic development and drug repurposing.  

The genetic variants affecting susceptibility and severity

The COVID-19 Host Genetics Initiative is an international network of researchers collaborating to map the genetic contributors to host susceptibility and response to COVID-19 infection. The group performed three genome-wide association meta-analyses using 46 genetic studies across 19 countries. Combined, this study involved 49,562 COVID-19 patients and more than 2 million controls from different genetic ancestries.

The researchers detected 13 genomic loci significantly associated with either SARS-CoV-2 infection or severe forms of COVID-19. Many of these loci overlapped with genes previously known to be associated with lung-related phenotypes or autoimmunity. For instance, TYK2 variants are known to protect against autoimmune diseases, while DPP9 and FOXP4 variants increase the risk of interstitial lung disease. These findings highlight the role of lung-related pathways in the progression of severe COVID-19.

Notably, variants in ABO, PPP1R15A and SLC6A20 were associated with susceptibility to infection, but not necessarily disease severity. Further studies would help determine the biological and clinical significance of these genetic loci in COVID-19.

A global effort to understand COVID-19

The authors highlighted the value of global representation in genetic studies. In fact, two of the novel loci underlying COVID-19 severity were detected only after including individuals of East Asian ancestry.

In this study, researchers have mapped the human genetic architecture of COVID-19, providing a framework for future studies to reveal novel pathogenic insights and new drug targets. Crucially, this provides a model for international collaboration that is needed in the effort to combat COVID-19.

Image credit: kjpargeter – Freepik

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covid-19 / Genetic Variants