Researchers identify genetic risk factors that contribute to the vulnerability and severity of pneumonia

Researchers at Vanderbilt University Medical Center and colleagues have identified genetic factors that increase the risk for developing influenza seizures and the side effects of life.

Their conclusions, recently published in the American Journal of Human Genetics, may help efforts to identify patients with COVID-19 who are most at risk for pneumonia, and enable earlier interventions to prevent serious illness and death.

Despite the availability of COVID-19 vaccines, it will take months to bring in enough people to bring the pandemic under control, experts predict. Meanwhile, thousands of Americans are hospitalized and die from COVID-19 every day.

This study is so important because we performed individual analyzes in participants of Caucasian as well as African ancestry to identify genetic risk factors that contribute to the vulnerability and severity of pneumonia. Combined with systemic racism and socioeconomic factors reported by others, these genetic risk differences may contribute to some of the differences we see in COVID-19 results. . “

Jennifer “Piper” Below, Ph.D., Associate Physician and Author of Corresponding Paper

The researchers conducted genome-wide association (GWAS) studies of more than 85,000 patients whose genetic information is stored in a BioUMU VUMC biobank and which has been linked to “de-identified” electronic health records that have been removal of personally identifiable information. GWAS can identify links between genetic changes and disease.

With colleagues from the University of North Carolina at Chapel Hill, Texas MD University Cancer Center in Houston, and Icahn School of Medicine at Mount Sinai in New York, VUMC researchers identified nearly 9,000 cases of seizures in patients of ancestry European, and 1,710 cases in patients of African ancestry.

The strongest association of pneumonia in patients of European ancestry was the gene that causes cystic fibrosis (CF). This infection causes extremely thick mucus leading to chest infections and progressive respiratory failure.

In patients of African ancestry, the strongest pneumonia association was the mutation caused by sickle cell disease (SCD), a red blood cell disorder that increases the risk for influenza-induced influenza, the flu and upper respiratory diseases.

Children with CF and SCD are at particular risk for severe infection if they contract COVID-19.

The researchers found that “carriers” that are not affected by CF but carry a copy of the CF gene were more likely to catch the seizure, while those that did not impact at SCD still carries a copy of the SCD mutation at greater risk for true arrest.

Further studies will be needed to determine whether these carriers also carry a “silent, elevated risk for adverse effects from COVID-19,” the researchers said.

To identify other genetic changes that increase the risk of pneumonia, they removed patients with CF and SCD from their study, repeated the GWAS, and used another method called PrediXcan, which binds gene expression data with symptoms and diseases in the electronic health record.

This time they found a difference associated with pneumonia in a gene called R3HCC1L in patients of European ancestry, and one near a gene called UQCRFS1 in patients of African ancestry. The molecular function of R3HCC1L is unclear, but deletion of the UQCRFS1 in mice disrupts part of their disease-fighting immune response.

“While our understanding of the genetic mechanisms of pneumonia remains limited, this study identified novel candidate genes, R3HCC1L and UQCRFS1, and provided insight for further host genetic studies on COVID-19,” said the paper’s first author, Hung- Hsin Chen, PhD, MS, graduate in Below laboratory.

“Our findings can be applied to identify the individuals at high risk of severe seizures and develop detailed treatment for them,” Chen said.