Por favor, use este identificador para citar o enlazar este ítem:
http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/222| Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis | |
| Shitao Rao Alexandria Lau Hon-Cheong So | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| 10.1101/2020.03.04.20031237 | |
| The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p<0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was partially supported by the Lo Kwee Seong Biomedical Research Fund, an NSFC grant and a Chinese University of Hong Kong Direct Grant. ### Author Declarations All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data are available from the IEU-GWAS and GTEx databases. GWAS summary statistics for diabetes is also available from the DIAGRAM Consortium website. | |
| Cold Spring Harbor Laboratory Press | |
| 2020 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/2020.03.04.20031237v1 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
Cargar archivos:
| Fichero | Tamaño | Formato | |
|---|---|---|---|
| Exploring deseases.pdf | 781.2 kB | Adobe PDF | Visualizar/Abrir |