Trans-ethnic genome-wide association study of severe COVID-19

Wu, Peng; Ding, Lin; Li, Xiaodong; Liu, Siyang; Cheng, Fanjun; He, Qing-Yu; Xiao, Mingzhong; Wu, Ping; Hou, Hongyan; Jiang, Minghui; Long, Pinpin; Wang, Hao; Liu, Linlin; Qu, Minghan; Shi, Xian; Jiang, Qin; Mo, Tingting; Ding, Wencheng; Fu, Yu; Han, Shi; Huo, Xixiang; Zeng, Yingchun; Zhou, Yue; Zhang, Qing; Ke, Jia; Xu, Xi; Ni, Wei; Shao, Zuoyu; Wang, Jing‐Zhi; Liu, Panhong; Li, Zilong; Jin, Yan; Zheng, Fang; Wang, Fang; Liu, Lei; Li, Wending; Liu, Kang; Peng, Rong; Xu, Xuedan; Lin, Yandan; Gao, Hui; Shi, Limei; Geng, Ziyue; Mu, Xuanwen; Yu, Yan; Wang, Kai; Wu, Degang; Hao, Xingjie; Cheng, Shanshan; Qiu, Gaokun; Guo, Huan; Li, Kezhen; Chen, Gang; Sun, Ziyong; Lin, Xihong; Jin, Xin; Wang, Feng; Sun, Chaoyang; Wang, Chaolong

doi:10.1038/s42003-021-02549-5

Cited by 29 publications

(25 citation statements)

References 68 publications

(80 reference statements)

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“…In response to the global COVID-19 outbreak, rapid efforts were directed towards unravelling the host genetic contribution to the susceptibility and severity of the disease. Several genome-wide association studies (GWAS) were conducted in ethnically-varied populations, which uncovered potential genomic biomarkers linked to an increased risk of infection and progression to severe clinical manifestations ( Severe Covid-19 GWAS Group., 2020 , Li et al, 2021 , Wu et al, 2021 , Mousa et al, 2021 Dec , Pairo-Castineira et al, 2021 Mar , Wang et al, 2020 Nov 10 , Hu et al, 2021 Feb 3 , Horowitz et al, 2021 ). Parallel to GWAS, which represent an indispensable approach for providing statistical evidence of association with susceptibility loci at genome level, several candidate gene-based, case-control association studies have recently been conducted, interrogating the role of specific gene variants in COVID-19 prognosis.…”

Section: Introductionmentioning

confidence: 99%

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

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Section: Introductionmentioning

confidence: 99%

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Gupta

Kaur²,

Pathak³

et al. 2022

Gene

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“…Over the past two years, GWAS has offered the opportunity to uncover genetic susceptibility factors for COVID-19 disease and provide insights into the biological basis of SARS-CoV-2 etiology. To date, a large number of risk genetic variants and genes have been identi ed by the GWAS approach, which has been intimately connected to the COVID-19 susceptibility and severity [32][33][34][35]48]. However, after merging all identi ed risk COVID-19 variants from GWAS Catalog with our WES data of dead patients, we identi ed only 3 common variants -a missense variant rs11147040, synonymous variant rs72472161, and coding sequence variant rs8176719.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, worldwide genome-wide association studies (GWAS) have identi ed many risk genes and loci that could be functionally implicated in COVID-19 disease [32][33][34][35][36]. Recent whole-exome sequencing (WES)-based studies in several countries also aimed to identify the genetic COVID-19 susceptibility factors.…”

Section: Introductionmentioning

confidence: 99%

Evaluation and Limitations of Different Approaches Among COVID-19 Fatal Cases Using Whole-exome Sequencing Data

Forgacova

Holesova

Hekel

et al. 2022

Preprint

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Background: COVID-19 caused by SARS-CoV-2 infection may result in various disease symptoms and severity, ranging from asymptomatic, through mild, up to very severe and fatal cases. Although environmental, clinical, and social factors play important roles in both susceptibility to SARS-CoV-2 infection and COVID-19 disease progress, it is becoming evident that both pathogen and host genetic factors are important too. Here we report whole-exome sequencing (WES) findings of 27 individuals who died as a result of COVID-19 infection, especially focusing on frequencies of DNA variants in genes previously associated with SARS-CoV-2 infection and COVID-19 severity. Results: We selected risk DNA variants/alleles or target genes using four different approaches: 1) aggregated GWAS results from the GWAS Catalog; 2) selected publications from PubMed; 3) the aggregated results of the Host Genetics Initiative database; and 4) a commercial DNA variant annotation/interpretation tool providing its own knowledgebase. We divided these variants/genes into those reported to influence the susceptibility to SARS-CoV-2 infection and those influencing COVID-19 severity. Based on these, we compared frequencies of alleles among the fatal COVID-19 cases to frequencies identified in two population control datasets (non-Finnish European population from the gnomAD database and genomic frequencies specific for the Slovak population from our own database). Our comparisons delineated a trend of higher frequencies of severe COVID-19 associated risk alleles among fatal COVID-19 cases, when compared to both control population datasets. This trend reached statistical significance specifically when using the HGI derived variant list. We also analyzed other approaches to WES data evaluation, where we showed their usage as well as limitations. Conclusions: Although our results proved the likely involvement of host genetic factors pinned out by previous studies for COVID-19 disease severity, careful considerations about the molecular-testing strategies and the evaluated genomic positions may have a strong impact on the utility of genomic testing.

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“…Genome-wide association study (GWAS) is a hypothesis-free approach suitable for the discovery of novel, common genetic markers. Genome-wide analyses have been focused on different COVID-19 outcomes, such as susceptibility to infection, severe disease, critical disease, and lethal outcome, as well as hospitalization rate, post-COVID-19 syndrome and response to COVID-19 vaccines ( COVID-19 Host Genetics Initiative, 2021 ; Pairo-Castineira et al, 2021 ; Wu et al, 2021 ; Thibord et al, 2022 ). The results of these studies have implicated several genome loci with a COVID-19 outcome.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Trans-ethnic genome-wide association study of severe COVID-19

Cited by 29 publications

References 68 publications

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Systematic review and meta-analysis of human genetic variants contributing to COVID-19 susceptibility and severity

Evaluation and Limitations of Different Approaches Among COVID-19 Fatal Cases Using Whole-exome Sequencing Data

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

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