Journal of Personalized Medicine (Nov 2021)
MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity
- Claudio Cappadona,
- Elvezia Maria Paraboschi,
- Nicole Ziliotto,
- Sandro Bottaro,
- Valeria Rimoldi,
- Alessio Gerussi,
- Andrea Azimonti,
- Daniele Brenna,
- Andrea Brunati,
- Charlotte Cameroni,
- Giovanni Campanaro,
- Francesca Carloni,
- Giacomo Cavadini,
- Martina Ciravegna,
- Antonio Composto,
- Giuseppe Converso,
- Pierluigi Corbella,
- Davide D’Eugenio,
- Giovanna Dal Rì,
- Sofia Maria Di Giorgio,
- Maria Chiara Grondelli,
- Lorenza Guerrera,
- Georges Laffoucriere,
- Beatrice Lando,
- Leandro Lopedote,
- Benedetta Maizza,
- Elettra Marconi,
- Carlotta Mariola,
- Guia Margherita Matronola,
- Luca Maria Menga,
- Giulia Montorsi,
- Antonio Papatolo,
- Riccardo Patti,
- Lorenzo Profeta,
- Vera Rebasti,
- Alice Smidili,
- Sofia Maria Tarchi,
- Francesco Carlo Tartaglia,
- Gaia Tettamanzi,
- Elena Tinelli,
- Riccardo Stuani,
- Cristiana Bolchini,
- Linda Pattini,
- Pietro Invernizzi,
- Frauke Degenhardt,
- Andre Franke,
- Stefano Duga,
- Rosanna Asselta
Affiliations
- Claudio Cappadona
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Elvezia Maria Paraboschi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Nicole Ziliotto
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Sandro Bottaro
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Valeria Rimoldi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Alessio Gerussi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Andrea Azimonti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Daniele Brenna
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Andrea Brunati
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Charlotte Cameroni
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Giovanni Campanaro
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Francesca Carloni
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Giacomo Cavadini
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Martina Ciravegna
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Antonio Composto
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Giuseppe Converso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Pierluigi Corbella
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Davide D’Eugenio
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Giovanna Dal Rì
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Sofia Maria Di Giorgio
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Maria Chiara Grondelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Lorenza Guerrera
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Georges Laffoucriere
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Beatrice Lando
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Leandro Lopedote
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Benedetta Maizza
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Elettra Marconi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Carlotta Mariola
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Guia Margherita Matronola
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Luca Maria Menga
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Giulia Montorsi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Antonio Papatolo
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Riccardo Patti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Lorenzo Profeta
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Vera Rebasti
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Alice Smidili
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Sofia Maria Tarchi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Francesco Carlo Tartaglia
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Gaia Tettamanzi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Elena Tinelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Riccardo Stuani
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Cristiana Bolchini
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
- Linda Pattini
- Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133 Milan, Italy
- Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
- Frauke Degenhardt
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany
- Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, 24105 Kiel, Germany
- Stefano Duga
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- Rosanna Asselta
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele, Italy
- DOI
- https://doi.org/10.3390/jpm11111166
- Journal volume & issue
-
Vol. 11,
no. 11
p. 1166
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Besides virus intrinsic characteristics, the host genetic makeup is predicted to account for the extreme clinical heterogeneity of the disease, which is characterized, among other manifestations, by a derangement of hemostasis associated with thromboembolic events. To date, large-scale studies confirmed that genetic predisposition plays a role in COVID-19 severity, pinpointing several susceptibility genes, often characterized by immunologic functions. With these premises, we performed an association study of common variants in 32 hemostatic genes with COVID-19 severity. We investigated 49,845 single-nucleotide polymorphism in a cohort of 332 Italian severe COVID-19 patients and 1668 controls from the general population. The study was conducted engaging a class of students attending the second year of the MEDTEC school (a six-year program, held in collaboration between Humanitas University and the Politecnico of Milan, allowing students to gain an MD in Medicine and a Bachelor’s Degree in Biomedical Engineering). Thanks to their willingness to participate in the fight against the pandemic, we evidenced several suggestive hits (p PROC, MTHFR, MTR, ADAMTS13, and THBS2 genes (top signal in PROC: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50–3.34, p = 8.77 × 10−5). The top signals in PROC, MTHFR, MTR, ADAMTS13 were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (p = 1.62 × 10−8 for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the MTHFR variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09–1.33, p = 4.34 × 10−14 in the weighted analysis).
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