Marko Zecevic1,2, Nikola Kotur1*, Bojan Ristivojevic1, Vladimir Gasic1, Branka Zukic1, Sonja Pavlovic1 and Biljana Stankovic1
1Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
2Seven Bridges, Boston, MA, United States
nikola.kotur [at] imgge.bg.ac.rs
Abstract
Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6,MRPL36, p = 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1,LURAP1L, p = 8.69 × 10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
Keywords: GWAS, SARS-CoV-2, genetic markers, pneumonia, severe disease
Acknowledgement: Genotyping of the samples was supported by COVID-19 Host Genetics Initiative. It was performed by the Human Genomics Facility of the Genetic Laboratory of the Department of Internal Medicine at Erasmus MC. Computational resources were provided by The Cancer Genomics Cloud, powered by Seven Bridges, a component of the NCI Cancer Research Data Commons (datacommons.cancer.gov), funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN261201400008C and ID/IQ Agreement No. 17X146 under Contract No. HHSN261201500003I.
