AUTHOR=Zecevic Marko , Kotur Nikola , Ristivojevic Bojan , Gasic Vladimir , Skodric-Trifunovic Vesna , Stjepanovic Mihailo , Stevanovic Goran , Lavadinovic Lidija , Zukic Branka , Pavlovic Sonja , Stankovic Biljana 

TITLE=Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.911010

DOI=10.3389/fgene.2022.911010

ISSN=1664-8021

ABSTRACT=<p>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 (<italic>n</italic> = 80) against patients without pneumonia (<italic>n</italic> = 48), and (2) severe (<italic>n</italic> = 34) against mild disease (<italic>n</italic> = 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 <italic>KLHL1</italic> (<italic>p</italic> = 1.91 × 10<sup>−8</sup>). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in <italic>SACM1L</italic> and <italic>LZTFL1</italic> genes suggestively associated with pneumonia (<italic>p</italic> = 7.54 × 10<sup>−6</sup>) and severe COVID-19 (<italic>p</italic> = 6.88 × 10<sup>−7</sup>), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (<italic>IRX, NDUFS6, MRPL36, p</italic> = 2.81 × 10<sup>−6</sup>), 5q11.2 (<italic>ESM1, p</italic> = 6.59 × 10<sup>−6</sup>), and 9p23 (<italic>TYRP1, LURAP1L</italic>, <italic>p</italic> = 8.69 × 10<sup>−6</sup>). 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.</p>