Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity

Show simple item record Fadista, Joao Kraven, Luke M. Karjalainen, Juha Andrews, Shea J. Geller, Frank Baillie, J. Kenneth Wain, Louise Jenkins, R. Gisli Feenstra, Bjarke 2021-07-12T09:02:01Z 2021-07-12T09:02:01Z 2021-03
dc.identifier.citation Fadista , J , Kraven , L M , Karjalainen , J , Andrews , S J , Geller , F , Baillie , J K , Wain , L , Jenkins , R G & Feenstra , B 2021 , ' Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity ' , EBioMedicine , vol. 65 , 103277 .
dc.identifier.other PURE: 164999411
dc.identifier.other PURE UUID: 9b4493d3-d4ad-4cdc-9280-b738613d0693
dc.identifier.other WOS: 000634284600006
dc.description.abstract Background: Idiopathic pulmonary fibrosis (IPF) is a complex lung disease, characterized by progressive lung scarring. Severe COVID-19 is associated with substantial pneumonitis and has a number of shared major risk factors with IPF. This study aimed to determine the genetic correlation between IPF and severe COVID-19 and assess a potential causal role of genetically increased risk of IPF on COVID-19 severity. Methods: The genetic correlation between IPF and COVID-19 severity was estimated with linkage disequilib-rium (LD) score regression. We performed a Mendelian randomization (MR) study for IPF causality in COVID-19. Genetic variants associated with IPF susceptibility (P Findings: We detected a positive genetic correlation of IPF with COVID-19 severity (rg=0.31 [95% CI 0.04-0.57], P = 0.023). The MR estimates for severe COVID-19 did not reveal any genetic association (OR 1.05, [95% CI 0.92-1.20], P = 0.43). However, outlier analysis revealed that the IPF risk allele rs35705950 at MUC5B had a dif-ferent effect compared with the other variants. When rs35705950 was excluded, MR results provided evidence that genetically increased risk of IPF has a causal effect on COVID-19 severity (OR 1.21, [95% CI 1.06-1.38], P = 4.24 x 10(-3)). Furthermore, the IPF risk-allele at MUC5B showed an apparent protective effect against COVID-19 hospitalization only in older adults (OR 0.86, [95% CI 0.73-1.00], P = 2.99 x 10(-2)) . Interpretation: The strongest genetic determinant of IPF, rs35705950 at MUC5B, seems to confer protection against COVID-19, whereas the combined effect of all other IPF risk loci seem to confer risk of COVID-19 severity. The observed effect of rs35705950 could either be due to protective effects of mucin over-produc-tion on the airways or a consequence of selection bias due to (1) a patient group that is heavily enriched for the rs35705950 T undertaking strict self-isolation and/or (2) due to survival bias of the rs35705950 non-IPF risk allele carriers. Due to the diverse impact of IPF causal variants on SARS-CoV-2 infection, with a possible selection bias as an explanation, further investigation is needed to address this apparent paradox between variance at MUC5B and other IPF genetic risk factors. (C) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ( en
dc.format.extent 8
dc.language.iso eng
dc.relation.ispartof EBioMedicine
dc.rights cc_by_nc_nd
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject Mendelian randomization
dc.subject Covid-19
dc.subject Idiopathic pulmonary fibrosis
dc.subject MUC5B
dc.subject Mucin
dc.subject 3111 Biomedicine
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title Shared genetic etiology between idiopathic pulmonary fibrosis and COVID-19 severity en
dc.type Article
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization University of Helsinki
dc.description.reviewstatus Peer reviewed
dc.relation.issn 2352-3964
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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