TY  - JOUR
AU  - Zecević, Marko
AU  - Kotur, Nikola
AU  - Ristivojević, Bojan
AU  - Gašić, Vladimir
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1515
AB  - 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 x 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 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 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.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Genetics
T1  - Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population
VL  - 13
DO  - 10.3389/fgene.2022.911010
ER  - 

@article{
author = "Zecević, Marko and Kotur, Nikola and Ristivojević, Bojan and Gašić, Vladimir and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Stevanović, Goran and Lavadinović, Lidija and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2022",
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 x 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 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 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.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Genetics",
title = "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population",
volume = "13",
doi = "10.3389/fgene.2022.911010"
}

Zecević, M., Kotur, N., Ristivojević, B., Gašić, V., Skodrić-Trifunović, V., Stjepanović, M., Stevanović, G., Lavadinović, L., Zukić, B., Pavlović, S.,& Stanković, B.. (2022). Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics
Frontiers Media Sa, Lausanne., 13.
https://doi.org/10.3389/fgene.2022.911010

Zecević M, Kotur N, Ristivojević B, Gašić V, Skodrić-Trifunović V, Stjepanović M, Stevanović G, Lavadinović L, Zukić B, Pavlović S, Stanković B. Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics. 2022;13.
doi:10.3389/fgene.2022.911010 .

Zecević, Marko, Kotur, Nikola, Ristivojević, Bojan, Gašić, Vladimir, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Stevanović, Goran, Lavadinović, Lidija, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population" in Frontiers in Genetics, 13 (2022),
https://doi.org/10.3389/fgene.2022.911010 . .

TY  - JOUR
AU  - Kotur, Nikola
AU  - Skakić, Anita
AU  - Klaassen, Kristel
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Zivković, Zorica
AU  - Ostojić, Olivera
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1439
AB  - Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Nutrition
T1  - Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
VL  - 8
DO  - 10.3389/fnut.2021.689419
ER  - 

@article{
author = "Kotur, Nikola and Skakić, Anita and Klaassen, Kristel and Gašić, Vladimir and Zukić, Branka and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Zivković, Zorica and Ostojić, Olivera and Stevanović, Goran and Lavadinović, Lidija and Pavlović, Sonja and Stanković, Biljana",
year = "2021",
abstract = "Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Nutrition",
title = "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity",
volume = "8",
doi = "10.3389/fnut.2021.689419"
}

Kotur, N., Skakić, A., Klaassen, K., Gašić, V., Zukić, B., Skodrić-Trifunović, V., Stjepanović, M., Zivković, Z., Ostojić, O., Stevanović, G., Lavadinović, L., Pavlović, S.,& Stanković, B.. (2021). Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fnut.2021.689419

Kotur N, Skakić A, Klaassen K, Gašić V, Zukić B, Skodrić-Trifunović V, Stjepanović M, Zivković Z, Ostojić O, Stevanović G, Lavadinović L, Pavlović S, Stanković B. Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition. 2021;8.
doi:10.3389/fnut.2021.689419 .

Kotur, Nikola, Skakić, Anita, Klaassen, Kristel, Gašić, Vladimir, Zukić, Branka, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Zivković, Zorica, Ostojić, Olivera, Stevanović, Goran, Lavadinović, Lidija, Pavlović, Sonja, Stanković, Biljana, "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity" in Frontiers in Nutrition, 8 (2021),
https://doi.org/10.3389/fnut.2021.689419 . .