{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nakanishi T"],"funding":["MEXT | Japan Society for the Promotion of Science","Public Health Agency of Canada","Cancer Research UK","Medical Research Council","Fonds de Recherche du Québec - Santé","National Institute for Health Research (NIHR)","Canada Foundation for Innovation","Wellcome Trust","Gouvernement du Canada | Canadian Institutes of Health Research"],"pagination":["6198"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10550956"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(1)"],"pubmed_abstract":["Alternative splicing generates functional diversity in isoforms, impacting immune response to infection. Here, we evaluate the causal role of alternative splicing in COVID-19 severity and susceptibility by applying two-sample Mendelian randomization to cis-splicing quantitative trait loci and the results from COVID-19 Host Genetics Initiative. We identify that alternative splicing in lung, rather than total expression of OAS1, ATP11A, DPP9 and NPNT, is associated with COVID-19 severity. MUC1 and PMF1 splicing is associated with COVID-19 susceptibility. Colocalization analyses support a shared genetic mechanism between COVID-19 severity with idiopathic pulmonary fibrosis at the ATP11A and DPP9 loci, and with chronic obstructive lung diseases at the NPNT locus. Last, we show that ATP11A, DPP"],"journal":["Nature communications"],"pubmed_title":["Alternative splicing in lung influences COVID-19 severity and respiratory diseases."],"pmcid":["PMC10550956"],"funding_grant_id":["221680/Z/20/Z","365825; 409511, 100558, 169303","C18281/A29019","22KJ1190, 22J30004, 23H02917","476575"],"pubmed_authors":["Richards JB","Willett J","Guillen-Guio B","Allen RJ","Zhou S","Adra D","Nakanishi T","Farjoun Y"],"additional_accession":[]},"is_claimable":false,"name":"Alternative splicing in lung influences COVID-19 severity and respiratory diseases.","description":"Alternative splicing generates functional diversity in isoforms, impacting immune response to infection. Here, we evaluate the causal role of alternative splicing in COVID-19 severity and susceptibility by applying two-sample Mendelian randomization to cis-splicing quantitative trait loci and the results from COVID-19 Host Genetics Initiative. We identify that alternative splicing in lung, rather than total expression of OAS1, ATP11A, DPP9 and NPNT, is associated with COVID-19 severity. MUC1 and PMF1 splicing is associated with COVID-19 susceptibility. Colocalization analyses support a shared genetic mechanism between COVID-19 severity with idiopathic pulmonary fibrosis at the ATP11A and DPP9 loci, and with chronic obstructive lung diseases at the NPNT locus. Last, we show that ATP11A, DPP","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Oct","modification":"2026-05-29T07:13:30.511Z","creation":"2024-11-15T01:39:35.833Z"},"accession":"S-EPMC10550956","cross_references":{"pubmed":["37794074"],"doi":["10.1038/s41467-023-41912-4"]}}