TY - JOUR
T1 - Genetic variants are identified to increase risk of COVID-19 related mortality from UK Biobank data
AU - Hu, Jianchang
AU - Li, Cai
AU - Wang, Shiying
AU - Li, Ting
AU - Zhang, Heping
N1 - Funding Information:
Partially funded by U.S. National Institutes of Health R01HG010171 and R01MH116527.
Funding Information:
Zhang?s research is supported in part by the U.S. National Institutes of Health (R01HG010171 and R01MH116527). This research has been conducted using the UK Biobank Resource under Application Number 42009. We thank the Yale Center for Research Computing for guidance and use of the research computing infrastructure.
Funding Information:
Zhang’s research is supported in part by the U.S. National Institutes of Health (R01HG010171 and R01MH116527). This research has been conducted using the UK Biobank Resource under Application Number 42009. We thank the Yale Center for Research Computing for guidance and use of the research computing infrastructure.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors. Methods: In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations. Results: We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2. Conclusions: Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.
AB - Background: The severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly heterogeneous. Studies have reported that males and some ethnic groups are at increased risk of death from COVID-19, which implies that individual risk of death might be influenced by host genetic factors. Methods: In this project, we consider the mortality as the trait of interest and perform a genome-wide association study (GWAS) of data for 1778 infected cases (445 deaths, 25.03%) distributed by the UK Biobank. Traditional GWAS fails to identify any genome-wide significant genetic variants from this dataset. To enhance the power of GWAS and account for possible multi-loci interactions, we adopt the concept of super variant for the detection of genetic factors. A discovery-validation procedure is used for verifying the potential associations. Results: We find 8 super variants that are consistently identified across multiple replications as susceptibility loci for COVID-19 mortality. The identified risk factors on chromosomes 2, 6, 7, 8, 10, 16, and 17 contain genetic variants and genes related to cilia dysfunctions (DNAH7 and CLUAP1), cardiovascular diseases (DES and SPEG), thromboembolic disease (STXBP5), mitochondrial dysfunctions (TOMM7), and innate immune system (WSB1). It is noteworthy that DNAH7 has been reported recently as the most downregulated gene after infecting human bronchial epithelial cells with SARS-CoV-2. Conclusions: Eight genetic variants are identified to significantly increase the risk of COVID-19 mortality among the patients with white British ancestry. These findings may provide timely clues and potential directions for better understanding the molecular pathogenesis of COVID-19 and the genetic basis of heterogeneous susceptibility, with potential impact on new therapeutic options.
KW - COVID-19
KW - GWAS
KW - Host genetic factors
KW - Mortality
KW - SARS-CoV-2
KW - UK Biobank
UR - http://www.scopus.com/inward/record.url?scp=85100336033&partnerID=8YFLogxK
U2 - 10.1186/s40246-021-00306-7
DO - 10.1186/s40246-021-00306-7
M3 - Journal article
C2 - 33536081
AN - SCOPUS:85100336033
SN - 1473-9542
VL - 15
SP - 1
EP - 10
JO - Human Genomics
JF - Human Genomics
IS - 1
M1 - 10
ER -