GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19.
Pairo-Castineira, E.; Rawlik, K.; Klaric, L.; Law, A.; Clohisey Hendry, S.; Baillie, J. K.
Show abstract
Pulmonary inflammation drives critical illness in Covid-19, 1;2 creating a clinically homogeneous extreme phenotype, which we have previously shown to be highly efficient for discovery of genetic associations. 3;4 Despite the advanced stage of illness, we have found that immunomodulatory therapies have strong beneficial effects in this group. 1;5 Further genetic discoveries may identify additional therapeutic targets to modulate severe disease. 6 In this new data release from the GenOMICC (Genetics Of Mortality in Critical Care) study we include new microarray genotyping data from additional critically-ill cases in the UK and Brazil, together with cohorts of severe Covid-19 from the ISARIC4C 7 and SCOURGE 8 studies, and meta-analysis with previously-reported data. We find an additional 14 new genetic associations. Many are in potentially druggable targets, in inflammatory signalling (JAK1, PDE4A), monocyte-macrophage differentiation (CSF2), immunometabolism (SLC2A5, AK5), and host factors required for viral entry and replication (TMPRSS2, RAB2A). As with our previous work, these results provide tractable therapeutic targets for modulation of harmful host-mediated inflammation in Covid-19.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Genome-wide analysis of longitudinal lung function and gas transfer in individuals with idiopathic pulmonary fibrosis 94%
- Clinical characteristics with inflammation profiling of Long-COVID and association with one-year recovery following hospitalisation in the UK: a prospective observational study 92%
- Polygenic Risk and Rare Variants in Endotypes of Idiopathic Pulmonary Fibrosis 91%
Similar papers in this journal
- Spatial Profiling of Lung SARS-CoV-2 and Influenza Virus Infection Dissects Virus-Specific Host Responses and Gene Signatures 91%
- Genome-wide association study of Idiopathic Pulmonary Fibrosis susceptibility using clinically-curated European-ancestry datasets 89%
- An individual participant data meta-analysis of prognostic blood biomarkers in IPF 89%
Similar papers in this journal
- Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis 93%
- Pulmonary Fibrosis after COVID-19 is Associated with Severity of Illness and Blood Leukocyte Telomere Length 91%
- The protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study 91%
Similar papers in this journal
- Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease 96%
- Exome sequencing and analysis of 44,028 British South Asians enriched for high autozygosity 93%
- Central role of glycosylation processes in human genetic susceptibility to SARS-CoV-2 infections with Omicron variants 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.