MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity.
Claudio CappadonaElvezia Maria ParaboschiNicole ZiliottoSandro BottaroValeria RimoldiAlessio GerussiAndrea AzimontiDaniele BrennaAndrea BrunatiCharlotte CameroniGiovanni CampanaroFrancesca CarloniGiacomo CavadiniMartina CiravegnaAntonio CompostoGiuseppe ConversoPierluigi CorbellaDavide D'EugenioGiovanna Dal RìSofia Maria Di GiorgioMaria Chiara GrondelliLorenza GuerreraGeorges LaffoucriereBeatrice LandoLeandro LopedoteBenedetta MaizzaElettra MarconiCarlotta MariolaGuia Margherita MatronolaLuca Maria MengaGiulia MontorsiAntonio PapatoloRiccardo PattiLorenzo ProfetaVera RebastiAlice SmidiliSofia Maria TarchiFrancesco Carlo TartagliaGaia TettamanziElena TinelliRiccardo StuaniCristiana BolchiniLinda PattiniInvernizzi PietroFrauke DegenhardtAndre FrankeStefano DugaRosanna AsseltaPublished in: Journal of personalized medicine (2021)
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 < 0.001), involving the 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).
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- coronavirus disease
- genome wide
- high school
- copy number
- bioinformatics analysis
- genome wide identification
- dna methylation
- computed tomography
- gene expression
- genome wide analysis
- randomized controlled trial
- clinical trial
- quality improvement
- mental health
- big data
- electronic health record
- single cell
- magnetic resonance imaging
- mass spectrometry
- tertiary care
- emergency department
- study protocol
- data analysis
- deep learning
- open label