Povysil Gundula, Butler-Laporte Guillaume, Shang Ning, Weng Chen, Khan Atlas, Alaamery Manal, Nakanishi Tomoko, Zhou Sirui, Forgetta Vincenzo, Eveleigh Robert, Bourgey Mathieu, Aziz Naveed, Jones Steven, Knoppers Bartha, Scherer Stephen, Strug Lisa, Lepage Pierre, Ragoussis Jiannis, Bourque Guillaume, Alghamdi Jahad, Aljawini Nora, Albes Nour, Al-Afghani Hani M, Alghamdi Bader, Almutair Mansour, Mahmoud Ebrahim Sabri, Safie Leen Abu, Bardisy Hadeel El, Al Harthi Fawz S, Alshareef Abdulraheem, Suliman Bandar Ali, Alqahtani Saleh, AlMalik Abdulaziz, Alrashed May M, Massadeh Salam, Mooser Vincent, Lathrop Mark, Arabi Yaseen, Mbarek Hamdi, Saad Chadi, Al-Muftah Wadha, Badji Radja, Al Thani Asma, Ismail Said I, Gharavi Ali G, Abedalthagafi Malak S, Richards J Brent, Goldstein David B, Kiryluk Krzysztof
Institute for Genomic Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Lady Davis Institute for Medical Research, Montréal, Québec, Canada.
medRxiv. 2020 Dec 21:2020.12.18.20248226. doi: 10.1101/2020.12.18.20248226.
A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,934 COVID-19 cases (713 with severe and 1,221 with mild disease) and 15,251 ancestry-matched population controls across four independent COVID-19 biobanks. We then tested if rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only one rare pLOF mutation across these genes amongst 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We find no evidence of association of rare loss-of-function variants in the proposed 13 candidate genes with severe COVID-19 outcomes.
最近的一份报告发现，在Toll样受体3（TLR3）和干扰素调节因子7（IRF7）依赖的I型干扰素途径中，13个候选基因的罕见预测功能丧失（pLOF）变异可解释高达3.5%的重症新冠肺炎病例。我们对来自四个独立新冠肺炎生物样本库的1934例新冠肺炎病例（713例重症和1221例轻症）以及15251例血统匹配的人群对照进行了全外显子组或全基因组测序。然后，我们测试了这13个基因中的罕见pLOF变异是否与重症新冠肺炎相关。在713例重症新冠肺炎病例中，我们仅在这些基因中发现了一个罕见的pLOF突变，并且与人群对照或轻症新冠肺炎病例相比，未观察到重症病例中pLOF的富集。我们没有发现所提出的13个候选基因中的罕见功能丧失变异与重症新冠肺炎结局相关的证据。
