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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/4744| 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. | |
| 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. | |
| www.medrxiv.org | |
| 2020 | |
| Artículo | |
| https://www.medrxiv.org/content/10.1101/2020.03.04.20031237v1.full.pdf | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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