Host genetic basis of COVID-19: from methodologies to genes.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
21
12
2021
accepted:
09
05
2022
revised:
04
04
2022
pubmed:
27
5
2022
medline:
6
8
2022
entrez:
26
5
2022
Statut:
ppublish
Résumé
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is having a massive impact on public health, societies, and economies worldwide. Despite the ongoing vaccination program, treating COVID-19 remains a high priority; thus, a better understanding of the disease is urgently needed. Initially, susceptibility was associated with age, sex, and other prior existing comorbidities. However, as these conditions alone could not explain the highly variable clinical manifestations of SARS-CoV-2 infection, the attention was shifted toward the identification of the genetic basis of COVID-19. Thanks to international collaborations like The COVID-19 Host Genetics Initiative, it became possible the elucidation of numerous genetic markers that are not only likely to help in explaining the varied clinical outcomes of COVID-19 patients but can also guide the development of novel diagnostics and therapeutics. Within this framework, this review delineates GWAS and Burden test as traditional methodologies employed so far for the discovery of the human genetic basis of COVID-19, with particular attention to recently emerged predictive models such as the post-Mendelian model. A summary table with the main genome-wide significant genomic loci is provided. Besides, various common and rare variants identified in genes like TLR7, CFTR, ACE2, TMPRSS2, TLR3, and SELP are further described in detail to illustrate their association with disease severity.
Identifiants
pubmed: 35618891
doi: 10.1038/s41431-022-01121-x
pii: 10.1038/s41431-022-01121-x
pmc: PMC9135575
doi:
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
899-907Informations de copyright
© 2022. The Author(s).
Références
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180:934–43.
Williams FMK, Freidin MB, Mangino M, Couvreur S, Visconti A, Bowyer RCE, et al. Self-reported symptoms of COVID-19, including symptoms most predictive of SARS-CoV-2 infection, are heritable. Twin Res Hum Genet. 2020;23:316–21. https://www.cambridge.org/core/journals/twin-research-and-human-genetics/article/abs/selfreported-symptoms-of-covid19-including-symptoms-most-predictive-of-sarscov2-infection-are-heritable/316C6D3F18A25A99B11572BA777606CC .
doi: 10.1017/thg.2020.85
de Castro MV, Silva MVR, Naslavsky MS, Santos KS, Magawa JY, Neto EC, et al. COVID-19 in twins: what can we learn from them? medRxiv [Preprint]. 2021 [cited 2022 April 1]: [5 p.]. Available from: https://doi.org/10.1101/2021.09.29.21263145 .
The Severe Covid-19 GWAS Group. Genomewide association study of severe COVID-19 with respiratory failure. N Engl J Med. 2020;383:1522–34.
doi: 10.1056/NEJMoa2020283
Pairo-Castineira E, Clohisey S, Klaric L, Bretherick AD, Rawlik K, Pasko D, et al. Genetic mechanisms of critical illness in covid-19. Nature. 2021;591:92–98.
doi: 10.1038/s41586-020-03065-y
COVID-19 Host Genetics Initiative. Mapping the human genetic architecture of COVID-19. Nature. 2021;600:472–7.
doi: 10.1038/s41586-021-03767-x
Kousathanas A, Pairo-Castineira E, Rawlik K, Stuckey A, Odhams CA, Walker S, et al. Whole genome sequencing identifies multiple loci for critical illness caused by COVID-19. medRxiv [Preprint]. 2021 [cited 2022 April 1]: [27 p.]. Available from: https://doi.org/10.1101/2021.09.02.21262965 .
Kousathanas A, Pairo-Castineira E, Rawlik K, Stuckey A, Odhams CA, Walker S, et al. Whole genome sequencing reveals host factors underlying critical Covid-19. Nature. 2022:1–10. Available from: https://www.nature.com/articles/s41586-022-04576-6 .
Kosmicki JA, Horowitz JE, Banerjee N, Lanche R, Marcketta A, Maxwell E, et al. Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals. Am J Hum Genet. 2021;108:1350–5.
doi: 10.1016/j.ajhg.2021.05.017
Molla M, Waddell M, Page D, Shavlik J. Using machine learning to design and interpret gene-expression microarrays. AIMag. 2004;25:23. https://ojs.aaai.org/index.php/aimagazine/article/view/1745 .
Uffelmann E, Huang QQ, Munung NS, de Vries J, Okada Y, Martin AR, et al. Genome-wide association studies. Nat Rev Dis Primers. 2021;1:59.
COVID-19 Host Genetics Initiative. [cited 2022 Apr]. Available from: https://www.covid19hg.org .
Guo MH, Plummer L, Chan Y-M, Hirschhorn JN, Lippincott MF. Burden testing of rare variants identified through exome sequencing via publicly available control data. Am J Hum Genet. 2018;103:522–34.
doi: 10.1016/j.ajhg.2018.08.016
Boyle EA, Li YI, Pritchard JK. An expanded view of complex traits: from polygenic to omnigenic. Cell. 2017;169:1177–86. https://www.cell.com/cell/fulltext/S0092-8674 .
doi: 10.1016/j.cell.2017.05.038
Marouli E, Graff M, Medina-Gomez C, Lo KS, Wood AR, Kjaer TR, et al. Rare and low-frequency coding variants alter human adult height. Nature. 2017;542:186–90. https://www.nature.com/articles/nature21039 .
doi: 10.1038/nature21039
Picchiotti N, Benetti E, Fallerini C, Daga S, Baldassarri M, Fava F, et al. Post-Mendelian genetic model in COVID-19. Cardiol Cardiovascular Med. 2021;5:673–94.
Fallerini C, Picchiotti N, Baldassarri M, Zguro K, Daga S, Fava F, et al. Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity. Hum Genet. 2021;141:147–73. https://doi.org/10.1007/s00439-021-02397-7 .
Zhang S, Cooper-Knock J, Weimer AK, Harvey C, Julian TH, Wang C, et al. Common and rare variant analyses combined with single-cell multiomics reveal cell-type-specific molecular mechanisms of COVID-19 severity. medRxiv [Preprint]. 2021 [cited 2022 April]: [82 p.]. Available from: https://doi.org/10.1101/2021.06.15.21258703 .
Hernández Cordero AI, Li X, Milne S, Yang CX, Bossé Y, Joubert P, et al. Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19. Hum Genet. 2021;140:969–79.
doi: 10.1007/s00439-021-02264-5
Andolfo I, Russo R, Lasorsa VA, Cantalupo S, Rosato BE, Bonfiglio F, et al. Common variants at 21q22.3 locus influence MX1 and TMPRSS2 gene expression and susceptibility to severe COVID-19. iScience. 2021;24:102322.
doi: 10.1016/j.isci.2021.102322
Ciancanelli MJ, Abel L, Zhang S-Y, Casanova J-L. Host genetics of severe influenza: from mouse Mx1 to human IRF7. Curr Opin Immunol. 2016;38:109–20.
doi: 10.1016/j.coi.2015.12.002
D’Antonio M, Nguyen JP, Arthur TD, Matsui H, D’Antonio-Chronowska A, Frazer KA. SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues. Cell Rep. 2021;37:110020.
doi: 10.1016/j.celrep.2021.110020
Monticelli M, Hay Mele B, Benetti E, Fallerini C, Baldassarri M, Furini S, et al. Protective role of a TMPRSS2 variant on severe COVID-19 outcome in young males and elderly women. Genes. 2021;12:596.
doi: 10.3390/genes12040596
Bongiovanni D, Klug M, Lazareva O, Weidlich S, Biasi M, Ursu S, et al. SARS-CoV-2 infection is associated with a pro-thrombotic platelet phenotype. Cell Death Dis. 2021;12:50.
Kaider A, Koder S, Panzer S, Pabinger I, Ay C, Jungbauer L, et al. P-selectin gene haplotypes modulate soluble P-selectin concentrations and contribute to the risk of venous thromboembolism. Thrombosis Haemost. 2008;99:899–904.
doi: 10.1160/TH07-11-0672
Fallerini C, Daga S, Benetti E, Picchiotti N, Zguro K, Catapano F, et al. SELP Asp603Asn and severe thrombosis in COVID-19 males. J Hematol Oncol. 2021;14:123.
Tregouet D-A. Specific haplotypes of the P-selectin gene are associated with myocardial infarction. Hum Mol Genet. 2002;11:2015–23.
doi: 10.1093/hmg/11.17.2015
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:683–90.
Kuo C, Pilling L, Atkins J, Kuchel G, Melzer D. ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants. Aging. 2020;12:12222–33.
doi: 10.18632/aging.103405
Kasparian K, Graykowski D, Cudaback E. Commentary: APOE e4 genotype predicts severe COVID-19 in the UK Biobank Community Cohort. Front Immunol. 2020;11:1939.
Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, et al. Toll-like receptor 3 signaling via TRIF contributes to a protective innate immune response to severe acute respiratory syndrome coronavirus infection. mBio. 2015;6:e00638–15.
Ranjith-Kumar CT, Miller W, Sun J, Xiong J, Santos J, Yarbrough I, et al. Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. J Biol Chem. 2007;282:17696–705.
doi: 10.1074/jbc.M700209200
Dhangadamajhi G, Rout R. Association of TLR3 functional variant (rs3775291) with COVID-19 susceptibility and death: a population-scale study. Hum Cell. 2021;34:1025–7.
Croci S, Venneri MA, Mantovani S, Fallerini C, Benetti E, Picchiotti N, et al. The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males. Autophagy. 2021;1–11.
Benetti E, Tita R, Spiga O, Ciolfi A, Birolo G, Bruselles A, et al. ACE2 gene variants may underlie interindividual variability and susceptibility to COVID-19 in the Italian population. Eur J Hum Genet. 2020;28:1602–14.
doi: 10.1038/s41431-020-0691-z
Ming Y, Qiang L Involvement of Spike protein, Furin, and ACE2 in SARS-CoV-2-related cardiovascular complications. SN Compr Clin Med. 2020;2:1103–8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352091/ .
Latini A, Agolini E, Novelli A, Borgiani P, Giannini R, Gravina P, et al. COVID-19 and genetic variants of protein involved in the SARS-CoV-2 entry into the host cells. Genes 2020;11:1010.
doi: 10.3390/genes11091010
Poulas K, Farsalinos K, Zanidis C. Activation of TLR7 and innate immunity as an efficient method against COVID-19 pandemic: imiquimod as a potential therapy. Front Immunol. 2020;11:1373.
van der Made CI, Simons A, Schuurs-Hoeijmakers J, van den Heuvel G, Mantere T, Kersten S, et al. Presence of genetic variants among young men with severe COVID-19. JAMA. 2020;324:663.
doi: 10.1001/jama.2020.13719
Fallerini C, Daga S, Mantovani S, Benetti E, Picchiotti N, Francisci D, et al. Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study. eLife. 2021;10:e67569.
Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science. 2020;24:eabd4570.
doi: 10.1126/science.abd4570
COVID Human Genetic Effort. [cited 2021 Dec]. Available from: https://www.covidhge.com/about .
Baldassarri M, Fava F, Fallerini C, Daga S, Benetti E, Zguro K, et al. Severe COVID-19 in hospitalized carriers of single CFTR pathogenic variants. J Personalized Med. 2021;11:558.
doi: 10.3390/jpm11060558
Sarantis P, Koustas E, Papavassiliou AG, Karamouzis MV. Are cystic fibrosis mutation carriers a potentially highly vulnerable group to COVID‐19? J Cell Mol Med. 2020;24:13542–5.
doi: 10.1111/jcmm.15941
Daga S, Fallerini C, Baldassarri M, Fava F, Valentino F, Doddato G, et al. Employing a systematic approach to biobanking and analyzing clinical and genetic data for advancing COVID-19 research. Eur J Hum Genet. 2021;29:745–59.
doi: 10.1038/s41431-020-00793-7
Mueller YM, Schrama TJ, Ruijten R, Schreurs MWJ, Grashof DGB, van de Werken HJG, et al. Immunophenotyping and machine learning identify distinct immunotypes that predict COVID-19 clinical severity. medRxiv [Preprint]. 2021 [cited 2022 April 1]: [28 p.]. Available from: https://doi.org/10.1101/2021.05.07.21256531 .
Riihimäki H, Chachólski W, Theorell J, Hillert J, Ramanujam R. A topological data analysis based classification method for multiple measurements. BMC Bioinformatics. 2020;21:336.
Rizvi AH, Camara PG, Kandror EK, Roberts TJ, Schieren I, Maniatis T, et al. Single-cell topological RNA-seq analysis reveals insights into cellular differentiation and development. Nat Biotechnol. 2017;35:551–60. https://www.nature.com/articles/nbt.3854 .
doi: 10.1038/nbt.3854
Neri G, Genuardi M. Genetica umana e medica. Milano: Edra; 2017. pp 129.
Mantovani S, Daga S, Fallerini C, Baldassarri M, Benetti E, Picchiotti N, et al. Rare variants in Toll-like receptor 7 results in functional impairment and downregulation of cytokine-mediated signaling in COVID-19 patients. Genes Immun. 2021;23:51–6.
doi: 10.1038/s41435-021-00157-1