Genetics Of Susceptibility To Viral Infection

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The severity of infectious diseases vary from person to person partly due to individual genetic factors. This can shape genetics at the population level, for example inherited sickle cell disease can protect against malarial infection, and is therefore advantageous in areas where malaria is endemic, while in other malaria-free areas it is a disadvantage. A more thorough generalized understanding of genetic determinants of infection could aid individual risk prediction and potentially provide leads for drug targets. Despite this, few genome wide association studies (GWAS) have investigated genetic links with infectious diseases.

Recognizing this John S. Witte of University of California San Francisco, and colleagues, evaluated the relationship between host genetics and antibody response to 28 antigens from 16 viruses that have been linked to cancer and neurodegenerative diseases with data from the UK biobank. The SARS-CoV-2 virus was also investigated. The results were released on the preprint server medRxiv.

A range of common viruses were present in the participants of the UK biobank, judged from a panel of 7924 participants. The SARS-CoV-2 virus was specifically screened for in 3002 participants. Of those that tested positive, 54% were men, 42% former smokers, and 12% self-identified as non-white compared to 8% of those who tested negative. Other health-related characteristics were similar, irrespective of the SARS-CoV-2 test outcome.

A significant association was found between SARS-CoV-2 infection and a variant of the ETS homologous factor gene on chromosome 11, part of the ETS transcription factor family with an epithelial-specific expression. Furthermore the variant conferred risk, increasing the likelihood of a positive test result. The expression of ACE2, the proposed primary receptor of SARS-CoV-2, was not clearly associated with SARS-CoV-2 infection in all tissues, including both positive and negative associations.


Two HLA variants were significantly protective against SARS-CoV-2, one of which was generally protective against viral infections. A number of genetic associations were made with other specific viral infections.

With regard to SARS-CoV-2 the study is limited in generalization by small sample size, the bias of the UK biobank for generally above average base-line health, and confounding.

“We performed genome-wide and transcriptome-wide association studies for serological phenotypes for 16 common viruses in a well-characterized, population-based cohort. We discovered novel genetic determinants of viral antibody response beyond the HLA region for BKV, MCV, HHV7, EBV EBNA, as well as SARS-CoV-2 infection status. Our comprehensive HLA analyses demonstrate that class II and III genes are crucial host genetic factors involved in regulating immune response to diverse viral antigens. Taken together, the findings of this work provide a resource for further understanding the complex interplay between viruses and the human genome, as well as a first step towards understanding germline determinants of SARS-CoV-2 infection,” stated the authors.