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New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations (preprint)
medrxiv; 2021.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2021.07.21.21260624
ABSTRACT
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Respiratory Insufficiency
/
COVID-19
Language:
English
Year:
2021
Document Type:
Preprint
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