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

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.

Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population

“…Several human GWAS studies have identified host genes and genetic loci associated with variation in SARS-CoV-2 disease severity and long-COVID [ 37 , 38 , 39 , 57 , 58 , 59 , 60 , 61 , 62 ]. Analysis of the impact of host genetic variation on SARS-CoV-2 vaccine-induced immunity has found associations between variant HLA alleles and variation in vaccine-induced antibody responses, vaccine breakthrough and vaccine side effects [ 63 , 64 ].…”

Micronutrients, genetics and COVID-19

“…These include old age, comorbidities, smoking, and low socioeconomic status. In addition, more than 20 loci throughout the genome have been associated with COVID-19 phenotypes in genome-wide association studies (GWAS) [1,2,3]. Big consortia, such as the Host Genetic Initiative (HGI) and UK Biobank (UKBB), analyzed data of thousands of patients with COVID-19 and healthy individuals to assess genetic factors predictive of infection vulnerability, hospitalization and severe disease [1,2].…”

Post-COVID condition: Pulmonary or systemic, reversible or irreversible?

“…Najsavremenija genetička ispitivanja obolelih od kovida sprovode se u mnogim zemljama, a nedavno su sprovedena i u srpskoj populaciji kod obolelih od kovida koji su hospitalno lečeni. Dobijeni rezultati sugerišu da postoje genetički markeri koji su jasni indikatori težih oblika bolesti, pre svega, težih kovid pneumonija, što se značajnim delom ogleda i u postkovid posledicama (18).…”