New research identifies 28 genetic regions linked to susceptibility and severity of COVID-19

A study published today in Nature unveils new genetic insights into COVID-19 susceptibility and severity. The paper, titled "A Second Update on Mapping the Human Genetic Architecture of COVID-19," marks a significant advancement in our understanding of the role genetics play in determining COVID-19 outcomes.

Led by the COVID-19 Host Genetics Initiative and spearheaded by Andrea Ganna (University of Helsinki), the research represents a remarkable collaborative effort involving experts from around the world, including researchers from the GCAT'Genomes for Life strategic project of the Germans Trias i Pujol Research Institute (IGTP).

The study delves deeper into the genetics of COVID-19, conducting a large genome-wide association study (GWAS) with an impressive sample size of more than 219,692 COVID-19 cases and more than 3 million controls. Overall, this second update identifies 51 significant genome-wide loci associated with both COVID-19 severity and SARS-CoV-2 susceptibility. These genetic loci provide valuable information about the disease, particularly concerning three main biological pathways that are crucial in determining susceptibility and severity of COVID-19: viral entry, the respiratory tract, and the immune system. In addition, advances in understanding the role of previous chronic conditions in the course of disease have been defined, allowing the identification of the most at-risk populations.

This update also builds upon earlier research by adding 28 new loci to the list of significant genetic factors, helping to complete the biology of the last and lethal global pandemics caused by the SARS-COV-2 virus. Pinpointing these genetic determinants is essential to understand the biological mechanisms that underlie the disease, to find effective treatments, and to protect potentially more vulnerable people.

This mega-analysis, built from a worldwide collaboration, the Host Initiative Consortium, has been important for several reasons. As Dr Rafael de Cid, Scientific Director of the GCAT Cohort at the IGPT, explains: "firstly, because of the impact in the knowledge about biology of the SARS-COV-2 pandemics, unveiling 51 genes in three major pathways, that could led to the identification of the mechanisms involved in the susceptibility and the severe course of the disease; second, because the study has established the grounds and the trustiness for a shared analysis, with an active and open transversal multi-layered-expertise forum from all the world, creating in this way the tools for the preparedness in future similar global challenges; and third, because it has shown that massive genetics is a powerful tool to dissect and understand the biology of a disease, even of an unknown disease as the COVID-19".

Specifically, "for GCAT and IGTP, the genome-wide association study (GWAS) on COVID-19 has paved the way for a large network of collaborations to study and deeply understand the biologic, environmental and social impact of the pandemic and its long terms consequences" adds De Cid. By setting up a large population-based study sourced from pre-pandemic data (the COVICAT cohort) to study prospectively the population after the first outbreak of the COVID-19 pandemic in Spain, contacted in 2020, re-contacted in 2021 and with a third wave of assessment running in 2023, long term effects of Long COVID are currently studied to understand this complex condition, identifying risk factors for the developing of the condition.

The paper's insights provide a critical foundation for personalized approaches to COVID-19 treatment and care. As researchers continue to uncover the complex interplay between genetics and disease outcomes, the potential for targeted therapies and interventions grows.

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About the COVID-19 Host Genetics Initiative:

The COVID-19 Host Genetics Initiative is a global collaborative endeavor dedicated to unraveling the genetic determinants of COVID-19 susceptibility and severity. The initiative brings together experts from diverse fields to contribute to the understanding of the genetic architecture underlying COVID-19 outcomes.

About GCAT'Genomes for Life Project:

The IGTP is a part of the consortium with GCAT, a population cohort of 20,000 people from across Catalonia. GCAT has contributed the analysed data of 5,000 participants to the study.

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Reference

The COVID-19 Host Genetics Initiative, Andrea Ganna et al. A second update on mapping the human genetic architecture of COVID-19. Nature. 2023 Sep 06 621:7-26. DOI: 10.1101/2022.12.24.22283874