Genome-wide epistasis study highlights genetic interactions influencing severity of COVID-19

被引：0

作者：

Shiqi Lin

Xingjian Gao

Frauke Degenhardt

Yu Qian

Tianzi Liu

Xavier Farre Ramon

Syed Sibte Hadi

Manuel Romero-Gómez

Javier Fernández

Agustín Albillos

Maria Buti Ferret

Luis Bujanda

Antonio Julià

Rafael de Cid

Rosanna Asselta

Andre Franke

Fan Liu

机构：

[1] Chinese Academy of Sciences and China National Center for Bioinformation,CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics

[2] University of Chinese Academy of Sciences,College of Life Sciences

[3] Jinling Hospital,National Clinical Research Center for Kidney Diseases

[4] Institute of Clinical Molecular Biology and University Hospital of Schleswig-Holstein,Genomes for Life

[5] Christian-Albrechts-University,GCAT Lab.

[6] Germans Trias i Pujol Research Institute (IGTP),Department of Forensic Sciences, College of Criminal Justice

[7] Naif Arab University of Security Sciences,Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD)

[8] Instituto de Salud Carlos III (ISCIII),Digestive Diseases Unit, Institute of Biomedicine of Seville

[9] Instituto de Biomedicina de Sevilla (IBIS),Department of Gastroenterology

[10] University of Sevilla,Liver Unit

[11] Virgen del Rocio University Hospital,Department of Liver and Gastrointestinal Diseases

[12] University of Seville,Vall d’Hebron Institut de Recerca (VHIR)

[13] Hospital Clinic,Department of Biomedical Sciences

[14] University of Barcelona,undefined

[15] and IDIBAPS,undefined

[16] European Foundation for the Study of Chronic Liver Failure (EF-CLIF),undefined

[17] Hospital Universitario Ramón y Cajal,undefined

[18] Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS),undefined

[19] University of Alcalá,undefined

[20] Hospital Universitari Vall d’Hebron,undefined

[21] Vall d’Hebron Barcelona Hospital Campus,undefined

[22] Universitat Autònoma de Barcelona,undefined

[23] Biodonostia Health Research Institute – Donostia University Hospital,undefined

[24] University of the Basque Country (UPV/EHU),undefined

[25] CIBERehd,undefined

[26] Ikerbasque,undefined

[27] Vall d’Hebron Hospital Universitari,undefined

[28] Humanitas University,undefined

[29] Humanitas Clinical and Research Center- IRCCS,undefined

来源：

European Journal of Epidemiology | 2023年 / 38卷 / 8期

关键词：

COVID-19; Severity; Genome-wide association study; Epistasis; UK Biobank; Gene–gene interaction;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may lead to life-threatening respiratory symptoms. Understanding the genetic basis of the prognosis of COVID-19 is important for risk profiling of potentially severe symptoms. Here, we conducted a genome-wide epistasis study of COVID-19 severity in 2243 patients with severe symptoms and 12,612 patients with no or mild symptoms from the UK Biobank, followed by a replication study in an independent Spanish cohort (1416 cases, 4382 controls). Our study highlighted 3 interactions with genome-wide significance in the discovery phase, nominally significant in the replication phase, and enhanced significance in the meta-analysis. For example, the lead interaction was found between rs9792388 upstream of PDGFRL and rs3025892 downstream of SNAP25, where the composite genotype of rs3025892 CT and rs9792388 CA/AA showed higher risk of severe disease than any other genotypes (P = 2.77 × 10–12, proportion of severe cases = 0.24 ~ 0.29 vs. 0.09 ~ 0.18, genotypic OR = 1.96 ~ 2.70). This interaction was replicated in the Spanish cohort (P = 0.002, proportion of severe cases = 0.30 ~ 0.36 vs. 0.14 ~ 0.25, genotypic OR = 1.45 ~ 2.37) and showed enhanced significance in the meta-analysis (P = 4.97 × 10–14). Notably, these interactions indicated a possible molecular mechanism by which SARS-CoV-2 affects the nervous system. The first exhaustive genome-wide screening for epistasis improved our understanding of genetic basis underlying the severity of COVID-19.

引用

页码：883 / 889

页数：6

共 28 条

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