Polygenic risk of idiopathic pulmonary fibrosis and COVID-19 severity

Abstract Introduction Coronavirus disease 2019 (COVID-19) survivors can develop residual lung abnormalities consistent with lung fibrosis. A shared genetic component between COVID-19 and idiopathic pulmonary fibrosis (IPF) has been shown. However, genetic overlap studies of IPF and COVID-19 have primarily concentrated on the IPF genome-wide significant risk variants that have been previously identified, rather than combined into a genome-wide polygenic risk. Here we used IPF genome-wide association study (GWAS) results to calculate polygenic risk scores (PRSs) and study their association with COVID-19 severity.Methods We used results from the largest meta-GWAS of clinically defined IPF risk (base dataset; n=24,589) and individual-level imputed data from the SCOURGE study of patients with COVID-19 (target dataset; n=15,024). We calculated IPF PRSs using PRSice-2 and assessed their association with COVID-19 hospitalisation, severe illness, and critical illness. We also evaluated the effect of age and sex stratification. Results were validated using an independent PRS method. Enrichment analyses and pathway-specific PRSs were performed to study biological pathways associated with COVID-19 severity.Results IPF PRSs were significantly associated with COVID-19 hospitalisation and severe illness. The strongest association was found in patients aged <60 years, especially among younger males (OR=1.16; 95%CI=1.08-1.25; p=6.39×10−5). A pathway enrichment analysis of the variants included in the best model fit and subsequent pathway-specific PRSs analyses supported the link of Cadherin and Integrin signalling pathways to COVID-19 severity when stratified by age and sex.Conclusion Our results suggest that there is genome-wide genetic overlap between IPF and severe COVID-19 that is dependent on age and sex and adds further support that the pathogenesis of both IPF and severe COVID-19 share underlying biological mechanisms. This could imply that individuals with a high IPF genetic risk are at an overall increased risk of developing lung sequelae resulting from severe COVID-19..

Medienart:	Preprint

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	bioRxiv.org - (2023) vom: 16. Juni Zur Gesamtaufnahme - year:2023

Sprache:	Englisch

Beteiligte Personen:	Guillen-Guio, Beatriz [VerfasserIn] Marcelino-Rodriguez, Itahisa [VerfasserIn] Lorenzo-Salazar, Jose Miguel [VerfasserIn] Leavy, Olivia C [VerfasserIn] Allen, Richard J [VerfasserIn] Riancho, José A. [VerfasserIn] Rojas, Augusto [VerfasserIn] Lapunzina, Pablo [VerfasserIn] Carracedo, Ángel [VerfasserIn] Wain, Louise V [VerfasserIn] Flores, Carlos [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.1101/2023.06.12.23291269

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PPN (Katalog-ID):	XBI039891208