3 research outputs found
Mapping the human genetic architecture of COVID-19
- Author
- Abdelrazik M.
- Abdullah T.
- Abe R.
- Abe S.
- Abecasis G. R.
- Abel L.
- Abernathy C.
- Abraheem A.
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- Zlatopolsky M.
- Zoller H.
- Zollner S.
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- Zucchi P.
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
Effects of Early Placement of Transjugular Portosystemic Shunts in Patients With High-Risk Acute Variceal Bleeding: a Meta-analysis of Individual Patient Data
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- Abraldes J. G.
- Albillos A.
- Alexandrino P.
- Allegretti G.
- Alvarado E.
- Amitrano L.
- Angrisani D.
- Appenrodt B.
- Augustin S.
- Bai W.
- Baiges A.
- Banares R.
- Barcelo R.
- Bosch J.
- Buceta E.
- Bureau C.
- Caca K.
- Calleja J. L.
- Canete N.
- Casanovas G.
- Casas M.
- Castellot A.
- Castellote J.
- Catalina M. -V.
- Cerda E.
- Conejo I.
- Cruz A.
- Dell'Era A.
- Di Pascoli M.
- Diaz R.
- Ding P.
- Dong J.
- Fan D.
- Ferlitsch A.
- Ferreira C. N.
- Ferrusquia-Acosta J.
- Fischer P.
- Garcia-Pagan J. C.
- Genesca J.
- Giraldez A.
- Gluud L. L.
- Gomez M. L.
- Gronbaek H.
- Guardascione M. A.
- Guevara C.
- Guo W.
- Haldrup D.
- Han G.
- Han N.
- He C.
- Hernandez-Gea V.
- Hernandez-Guerra M.
- Horia Stefanescu
- Ibanez-Samaniego L.
- Jansen C.
- Jiang Z.
- Jimenez E.
- Krag A.
- La Mura V.
- Laleman W.
- Laursen S. B.
- Li K.
- Li X.
- Li Y.
- Llop E.
- Luca A.
- Luo B.
- Luo J.
- Lv Y.
- Ma F.
- Macedo G.
- Magaz M.
- Marrero J. M.
- Martinez J.
- Martinez-Lagares F.
- Masnou H.
- Meireles L.
- Monescillo A.
- Mossner J.
- Moura M.
- Mundi J. L.
- Navascues C.
- Nevens F.
- Nicoara-Farcau O.
- Nie Y.
- Niu J.
- Palazon J. M.
- Pena E.
- Penate M.
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- Pop A.
- Primignani M.
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- Tellez L.
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- Wang G.
- Wang Q.
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- Zhang M.
- Zhang W.
- Zhao J.
- Zhong J.
- Zhu X.
- Zhu Y.
- Zhuge Y.
- Zipprich A.
- Zuo L.
- Publication venue
- 'Elsevier BV'
- Publication date
- 01/01/2021
- Field of study
No full textBackground & Aims: Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS. Methods: We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients. Results: Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323\u20130.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307\u20130.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253\u20130.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy. Conclusions: In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy
Mapping the human genetic architecture of COVID-19
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- Abdelrazik M
- Abdullah T
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- Abecasis GR
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- Abernathy C
- Abraheem A
- Abul-Husn NS
- Acosta-Herrera M
- Acquilini D
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- Adachi T
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- Alasdair F
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- Costantino G
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- zu Bentrup FM
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- Zwinderman AHK
- Zyndorf M
- Publication venue
- Publication date
- 01/01/2021
- Field of study
Get PDFThe genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease
