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重症Covid-19呼吸衰竭的全基因组关联研究
作者:小柯机器人 发布时间:2020/6/18 22:03:18

德国基督教阿尔布雷希茨大学Andre Franke联合挪威奥斯陆大学Tom H. Karlsen合作取得新进展。他们对重症Covid-19呼吸衰竭进行了全基因组关联研究。该成果发表在2020年6月17日出版的《新英格兰医学杂志》上。

在感染SARS-CoV-2的患者中,疾病行为存在很大差异,该病毒导致了Covid-19。全基因组关联分析可能有助于识别与Covid-19发育相关的潜在遗传因素。

研究组在意大利和西班牙的七家医院进行了一项全基因组关联研究,涉及1980名Covid-19重症(定义为呼吸衰竭)患者。在进行质量控制和排除人群离群值后,最终分析包括意大利的835名患者和1255名对照参与者,以及西班牙的775名患者和950名对照参与者。研究组共分析了8582968个单核苷酸多态性。

研究组在两个病例对照小组的荟萃分析中,检测到基因座3p21.31处的rs11385942和基因座9q34.2处的rs657152存在交叉复制关联,这在全基因组水平上具有显著意义。在基因座3p21.31,关联信号跨越基因SLC6A20、LZTFL1、CCR9、FYCO1、CXCR6和XCR1。9q34.2位点的关联信号与ABO血型位点一致。在该队列中,针对血型的分析显示,与其他血型相比,A型血的风险更高,比值比为1.45;O型血具有保护作用,比值比为0.65。

总之,研究组确定3p21.31基因簇为Covid-19呼吸衰竭患者的遗传易感基因座,并证实与ABO血型系统相关。

附:英文原文

Title: Genomewide Association Study of Severe Covid-19 with Respiratory Failure

Author: David Ellinghaus, Ph.D.,, Frauke Degenhardt, M.Sc.,, Luis Bujanda, M.D., Ph.D.,, Maria Buti, M.D., Ph.D.,, Agustín Albillos, M.D., Ph.D.,, Pietro Invernizzi, M.D., Ph.D.,, Javier Fernández, M.D., Ph.D.,, Daniele Prati, M.D.,, Guido Baselli, Ph.D.,, Rosanna Asselta, Ph.D.,, Marit M. Grimsrud, M.D.,, Chiara Milani, Ph.D.,, Fátima Aziz, B.S.,, Jan Kssens, Ph.D.,, Sandra May, Ph.D.,, Mareike Wendorff, M.Sc.,, Lars Wienbrandt, Ph.D.,, Florian Uellendahl-Werth, M.Sc.,, Tenghao Zheng, M.D., Ph.D.,, Xiaoli Yi,, Raúl de Pablo, M.D., Ph.D.,, Adolfo G. Chercoles, B.S.,, Adriana Palom, M.S., B.S.,, Alba-Estela Garcia-Fernandez, B.S.,, Francisco Rodriguez-Frias, M.S., Ph.D.,, Alberto Zanella, M.D.,, Alessandra Bandera, M.D., Ph.D.,, Alessandro Protti, M.D.,, Alessio Aghemo, M.D., Ph.D.,, Ana Lleo, M.D., Ph.D.,, Andrea Biondi, M.D.,, Andrea Caballero-Garralda, M.S., Ph.D.,, Andrea Gori, M.D.,, Anja Tanck,, Anna Carreras Nolla, B.S.,, Anna Latiano, Ph.D.,, Anna Ludovica Fracanzani, M.D.,, Anna Peschuck,, Antonio Julià, Ph.D.,, Antonio Pesenti, M.D.,, Antonio Voza, M.D.,, David Jiménez, M.D., Ph.D.,, Beatriz Mateos, M.D., Ph.D.,, Beatriz Nafria Jimenez, B.S.,, Carmen Quereda, M.D., Ph.D.,, Cinzia Paccapelo, M.Sc.,, Christoph Gassner, Ph.D.,, Claudio Angelini, M.D.,, Cristina Cea, B.S.,, Aurora Solier, M.D.,, David Pestaa, M.D., Ph.D.,, Eduardo Muiz-Diaz, M.D., Ph.D.,, Elena Sandoval, M.D.,, Elvezia M. Paraboschi, Ph.D.,, Enrique Navas, M.D., Ph.D.,, Félix García Sánchez, Ph.D.,, Ferruccio Ceriotti, M.D.,, Filippo Martinelli-Boneschi, M.D., Ph.D.,, Flora Peyvandi, M.D., Ph.D.,, Francesco Blasi, M.D., Ph.D.,, Luis Téllez, M.D., Ph.D.,, Albert Blanco-Grau, B.S., M.S.,, Georg Hemmrich-Stanisak, Ph.D.,, Giacomo Grasselli, M.D.,, Giorgio Costantino, M.D.,, Giulia Cardamone, Ph.D.,, Giuseppe Foti, M.D.,, Serena Aneli, Ph.D.,, Hayato Kurihara, M.D.,, Hesham ElAbd, M.Sc.,, Ilaria My, M.D.,, Iván Galván-Femenia, M.Sc.,, Javier Martín, M.D., Ph.D.,, Jeanette Erdmann, Ph.D.,, Jose Ferrusquía-Acosta, M.D.,, Koldo Garcia-Etxebarria, Ph.D.,, Laura Izquierdo-Sanchez, B.S.,, Laura R. Bettini, M.D.,, Lauro Sumoy, Ph.D.,, Leonardo Terranova, Ph.D.,, Leticia Moreira, M.D., Ph.D.,, Luigi Santoro, M.S.,, Luigia Scudeller, M.D.,, Francisco Mesonero, M.D.,, Luisa Roade, M.D.,, Malte C. Rühlemann, Ph.D.,, Marco Schaefer, Ph.D.,, Maria Carrabba, M.D., Ph.D.,, Mar Riveiro-Barciela, M.D., Ph.D.,, Maria E. Figuera Basso,, Maria G. Valsecchi, Ph.D.,, María Hernandez-Tejero, M.D.,, Marialbert Acosta-Herrera, Ph.D.,, Mariella D’Angiò, M.D.,, Marina Baldini, M.D.,, Marina Cazzaniga, M.D.,, Martin Schulzky, M.A.,, Maurizio Cecconi, M.D., Ph.D.,, Michael Wittig, M.Sc.,, Michele Ciccarelli, M.D.,, Miguel Rodríguez-Gandía, M.D.,, Monica Bocciolone, M.D.,, Monica Miozzo, Ph.D.,, Nicola Montano, M.D., Ph.D.,, Nicole Braun,, Nicoletta Sacchi, Ph.D.,, Nilda Martínez, M.D.,, Onur zer, M.Sc.,, Orazio Palmieri, Ph.D.,, Paola Faverio, M.D.,, Paoletta Preatoni, M.D.,, Paolo Bonfanti, M.D.,, Paolo Omodei, M.D.,, Paolo Tentorio, M.S.,, Pedro Castro, M.D., Ph.D.,, Pedro M. Rodrigues, Ph.D.,, Aaron Blandino Ortiz, M.D.,, Rafael de Cid, Ph.D.,, Ricard Ferrer, M.D.,, Roberta Gualtierotti, M.D.,, Rosa Nieto, M.D.,, Siegfried Goerg, M.D.,, Salvatore Badalamenti, M.D., Ph.D.,, Sara Marsal, Ph.D.,, Giuseppe Matullo, Ph.D.,, Serena Pelusi, M.D.,, Simonas Juzenas, Ph.D.,, Stefano Aliberti, M.D.,, Valter Monzani, M.D.,, Victor Moreno, Ph.D.,, Tanja Wesse,, Tobias L. Lenz, Ph.D.,, Tomas Pumarola, M.D., Ph.D.,, Valeria Rimoldi, Ph.D.,, Silvano Bosari, M.D.,, Wolfgang Albrecht,, Wolfgang Peter, Ph.D.,, Manuel Romero-Gómez, M.D., Ph.D.,, Mauro D’Amato, Ph.D.,, Stefano Duga, Ph.D.,, Jesus M. Banales, Ph.D.,, Johannes R Hov, M.D., Ph.D.,, Trine Folseraas, M.D., Ph.D.,, Luca Valenti, M.D.,, Andre Franke, Ph.D.,, and Tom H. Karlsen, M.D., Ph.D.

Issue&Volume: 2020-06-17

Abstract: BACKGROUND

There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19.

METHODS

We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels.

RESULTS

We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×108) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×1010; and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×108, respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×104) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×105).

CONCLUSIONS

We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system.

DOI: 10.1056/NEJMoa2020283

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2020283

 

 

 

 

 

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home