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Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization

Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genom...

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Autores principales: Luo, Yu-Si, Li, Wei, Cai, Yi, Zhang, Jingxuan, Gui, Hongsheng, Zhang, Ke, Cheng, Zhong-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637711/
https://www.ncbi.nlm.nih.gov/pubmed/36353114
http://dx.doi.org/10.3389/fgene.2022.1014191
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author Luo, Yu-Si
Li, Wei
Cai, Yi
Zhang, Jingxuan
Gui, Hongsheng
Zhang, Ke
Cheng, Zhong-Shan
author_facet Luo, Yu-Si
Li, Wei
Cai, Yi
Zhang, Jingxuan
Gui, Hongsheng
Zhang, Ke
Cheng, Zhong-Shan
author_sort Luo, Yu-Si
collection PubMed
description Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genome-wide association study (GWAS), the searching for sex-biased genetic variants showing differential association signals between sexes with COVID-19 hospitalization was severely hindered. We hypothesized genetic variants would show potentially sex-biased genetic effects on COVID-19 hospitalization if they display significant differential association effect sizes between male and female COVID-19 patients. By integrating two COVID-19 GWASs, including hospitalized COVID-19 patients vs. general population separated into males (case = 1,917 and control = 221,174) and females (case = 1,343 and control = 262,886), we differentiated the association effect sizes of each common single nucleotide polymorphism (SNP) within the two GWASs. Twelve SNPs were suggested to show differential COVID-19 associations between sexes. Further investigation of genes (n = 58) close to these 12 SNPs resulted in the identification of 34 genes demonstrating sex-biased differential expression in at least one GTEx tissue. Finally, 5 SNPs are mapped to 8 genes, including rs1134004 (GADD45G), rs140657166 (TRIM29 and PVRL1), rs148143613 (KNDC1 and STK32C), rs2443615 (PGAP2 and TRIM21), and rs2924725 (CSMD1). The 8 genes display significantly differential gene expression in blood samples derived from COVID-19 patients compared to healthy controls. These genes are potential genetic factors contributing to sex differences in COVID-19 hospitalization and warranted for further functional studies.
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spelling pubmed-96377112022-11-08 Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization Luo, Yu-Si Li, Wei Cai, Yi Zhang, Jingxuan Gui, Hongsheng Zhang, Ke Cheng, Zhong-Shan Front Genet Genetics Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genome-wide association study (GWAS), the searching for sex-biased genetic variants showing differential association signals between sexes with COVID-19 hospitalization was severely hindered. We hypothesized genetic variants would show potentially sex-biased genetic effects on COVID-19 hospitalization if they display significant differential association effect sizes between male and female COVID-19 patients. By integrating two COVID-19 GWASs, including hospitalized COVID-19 patients vs. general population separated into males (case = 1,917 and control = 221,174) and females (case = 1,343 and control = 262,886), we differentiated the association effect sizes of each common single nucleotide polymorphism (SNP) within the two GWASs. Twelve SNPs were suggested to show differential COVID-19 associations between sexes. Further investigation of genes (n = 58) close to these 12 SNPs resulted in the identification of 34 genes demonstrating sex-biased differential expression in at least one GTEx tissue. Finally, 5 SNPs are mapped to 8 genes, including rs1134004 (GADD45G), rs140657166 (TRIM29 and PVRL1), rs148143613 (KNDC1 and STK32C), rs2443615 (PGAP2 and TRIM21), and rs2924725 (CSMD1). The 8 genes display significantly differential gene expression in blood samples derived from COVID-19 patients compared to healthy controls. These genes are potential genetic factors contributing to sex differences in COVID-19 hospitalization and warranted for further functional studies. Frontiers Media S.A. 2022-10-24 /pmc/articles/PMC9637711/ /pubmed/36353114 http://dx.doi.org/10.3389/fgene.2022.1014191 Text en Copyright © 2022 Luo, Li, Cai, Zhang, Gui, Zhang and Cheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Luo, Yu-Si
Li, Wei
Cai, Yi
Zhang, Jingxuan
Gui, Hongsheng
Zhang, Ke
Cheng, Zhong-Shan
Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title_full Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title_fullStr Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title_full_unstemmed Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title_short Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization
title_sort genome-wide screening of sex-biased genetic variants potentially associated with covid-19 hospitalization
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9637711/
https://www.ncbi.nlm.nih.gov/pubmed/36353114
http://dx.doi.org/10.3389/fgene.2022.1014191
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