Genetic analysis reveals novel traits associated with COVID-19 severity

Researchers in the United States have conducted genetic correlation studies revealing novel traits associated with the development of severe coronavirus disease 2019 (COVID-19).

The team’s analysis validated previous epidemiology-based findings that health conditions such as hypertension and type 2 diabetes are associated with more severe COVID-19.

However, the researchers also discovered novel risk factors that have not previously been reported by epidemiology-based studies.

For example, they found that lower levels of educational attainment correlated with severe COVID-19 and hospitalization.

The team – from the Children’s Hospital of Philadelphia and the University of Pennsylvania – also found that opioid use and panic attacks appeared to be correlated with severe COVID 19 and hospitalization

“Taken together, this study extends our understanding of the genetic basis of COVID-19, and provides target traits for further epidemiological studies,” writes Hakon Hakonarson and colleagues.

A pre-print version of the paper is available on the medRxiv* server, while the article undergoes peer review.

Underlying health conditions increased risk of poor outcomes

The ongoing COVID-19 pandemic poses a particular threat to people with underlying medical conditions such as obesity, hypertension, and diabetes, since these conditions increase the risk of poor clinical outcomes.

Hakonarson and colleagues say that given the high genetic heritability of such conditions, they may share genetic factors that play an important role in the risk for severe disease.

Furthermore, a recent genome-wide association study (GWAS) of COVID-19 reported two genomic loci that were associated with severe disease, suggesting that disease severity is indeed strongly influenced by genetic components.

What did the researchers do?

The team analyzed the summary statistics of GWAS results released by the COVID-19 Host Genetics Initiative, the UK biobank and the GWAS Catalog to investigate the genetic overlap between COVID-19 and a wide range of traits and diseases.

The researchers explored genetic correlations between COVID-19 and 1,555 diseases and traits from UK biobank data.

The findings are consistent with those of epidemiologic studies showing that body mass index (BMI), for example, is significantly associated with severe disease or hospitalization.

Hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and heart disease were also correlated with COVID-19 severity, although these correlations did not reach statistical significance.

In addition, diseases of the circulatory, digestive and musculoskeletal systems were significantly associated with severe disease or hospitalization.

In agreement with these findings, the use of several medications taken for diabetes, obesity hypertension and digestive disease modestly correlated with COVID-19.

In particular, the use of an opioid medication called Tramadol strongly correlated with COVID-19 hospitalization.

“We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity,” writes the team.

Novel traits associated with COVID-19 risk were also observed

However, the team also observed novel traits that were associated with COVID-19 severity.

For example, significant negative correlation was observed between COVID-19 hospitalization and traits related to educational attainment such as college or university degree and intelligence scores.

Panic attacks were also significantly correlated with COVID-19 requiring hospitalization.

What did the GWAS Catalog 4 data show?

Next, the team estimated genetic correlations between COVID-19 and 80 diseases and traits from GWAS Catalog 4.

Consistent with findings from the UK biobank data, hypertension, and type 2 diabetes were associated with severe disease or hospitalization. Coronary artery disease, heart failure and BMI were also modestly associated with severe disease.

Similarly, the use of medications taken for obesity, diabetes, hypertension and digestive disease were modestly associated with COVID-19.

Interestingly, a significant negative correlation was again observed between educational attainment and COVID-19 hospitalization. Further analyses revealed that COVID-19 significantly correlated with cognitive performance and verbal-numerical reasoning.

The researchers suggest that this observation may reflect an indirect association mediated by human behavior.

“For example, patients with different educational levels may differ in diet choices (BMI) or smoking status,” they write.

Furthermore, the analysis of GWAS Catalog 4 data also revealed a significant correlation between the use of opioids and severe COVID-19 or hospitalization.

As side effects associated with chronic opioid use at high doses may affect the immune system and increase the risk of pneumonia, there is an urgent need to evaluate the relationship between COVID-19 severity and opioid use by epidemiological studies,” writes the team.

“Epidemiological studies are warranted to further evaluate these findings”

The researchers say the results confirm previous epidemiology-based findings that underlying health conditions such as hypertension, type 2 diabetes and obesity are associated with COVID-19 severity.

However, “we also report novel traits associated with COVID-19, which have not been previously reported from epidemiological data, such as opioid use and educational attainment,” they add.

This study provides novel information on underlying conditions that might increase the risk of severe illness of COVID-19. Added epidemiological studies are warranted to further evaluate these findings,” concludes the team.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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