Genetic predisposition to severe infectious diseases, with a special focus on archaic gene variants

An obvious question, which has been higlighted during the current pandemic, is why some people suffer from a mild illness while other experience a more severe course of an infectious disease. Some risk factors such high age and metabolic diseases were early identified in the pandemic. However, these risk factors only partially explain the differences in outcome.

Thus, genetic variation of the host needs to be investigated.

The COVID-19 pandemic brought acute attention to the Neanderthal genome when we showed that the major genetic risk factor for COVID-19 is inherited from Neanderthals (Zeberg & Pääbo, Nature 587: 610–612, 2020).

Strikingly, about one in three patients with severe COVID-19 carry the Neanderthal risk variant (Tomoko et al. medRxiv 03.07, 2021).

Moreover, we also identified a variant protective against COVID-19 inherited from Neanderthals (Zeberg & Pääbo, PNAS 118, 2021). A third variant in the cluster involving Toll-like receptors has also attracted our attention.

Using different techniques we will in the proposed project investigate how genetic variants inherited from archaic humans influence the outcome of infectious diseases.

In addition to bioinformatics, we will perform functional studies using gene editing, transcriptomics and heterologous expression of the gene variants in different cell types.

Illuminating how variation in host genetics affect disease outcomes will allow for risk stratification and suggest targets for drug development.