{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:04:15Z","timestamp":1784916255508,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012222","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000}}],"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009187","name":"Medical Research Foundation","doi-asserted-by":"publisher","award":["MC_UU_00035\/7"],"award-info":[{"award-number":["MC_UU_00035\/7"]}],"id":[{"id":"10.13039\/501100009187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"publisher","award":["SGL028\\1022"],"award-info":[{"award-number":["SGL028\\1022"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chief Scientist Office","award":["PCL\/20\/\/02"],"award-info":[{"award-number":["PCL\/20\/\/02"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Common genetic variants contribute to risk for complex human diseases. However, despite thousands of associations, variants modulating disease risk and their functional impact remain largely unknown. This includes SARS-CoV-2 infection, where outcomes range from asymptomatic to fatal. Most genetic risk variants associated with COVID-19 disease, identified through genome wide association studies, are located in the non-coding genome and may function by altering gene expression in disease-relevant cells and tissues. To address this at scale, we tested &gt;4800 severe COVID-19-associated variants to determine the impact of individual variants and variant combinations on regulatory activity using Self-Transcribing Active Regulatory Region sequencing, a massively-parallel reporter assay. Focusing on variants that may have their impact in the lung, in a lung epithelial cell line (A549) we identify 166 variants within active sequences, of which 29 modulate activity allele-specifically. Evaluating variant combinations, we observe both additive and non-additive effects on regulatory activity. We employ state-of-the-art deep learning models to interpret allele-specific variant effects on regulatory activity and endogenous genomic features. Our work provides a set of prioritised severe COVID-19-associated variants that modulate regulatory activity in lung epithelial cells, candidate transcription factors, and candidate target genes with potential to be disease modifying.<\/jats:p>","DOI":"10.1371\/journal.pgen.1012222","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:51:49Z","timestamp":1784310709000},"page":"e1012222","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying severe COVID-19 risk variants modulating enhancer reporter activity in lung cells"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2048-4796","authenticated-orcid":true,"given":"Giovanna","family":"Weykopf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6660-7735","authenticated-orcid":true,"given":"Wendy A.","family":"Bickmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Biddie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9944-6560","authenticated-orcid":true,"given":"Elias T.","family":"Friman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"pgen.1012222.ref001","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3390\/v15010175","article-title":"Risk factors of severe COVID-19: a review of host, viral and environmental factors","volume":"15","author":"L Zsichla","year":"2023","journal-title":"Viruses"},{"key":"pgen.1012222.ref002","first-page":"1","article-title":"Whole genome sequencing reveals host factors underlying critical Covid-19","author":"A Kousathanas","year":"2022","journal-title":"Nature"},{"issue":"7962","key":"pgen.1012222.ref003","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1038\/s41586-023-06034-3","article-title":"GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19","volume":"617","author":"E Pairo-Castineira","year":"2023","journal-title":"Nature"},{"key":"pgen.1012222.ref004","unstructured":"COVID-19 Host Genetics Initiative. A second update on mapping the human genetic architecture of COVID-19. Nature. 2023;621:E7\u2013E26."},{"issue":"1","key":"pgen.1012222.ref005","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41467-023-44250-7","article-title":"Estimating the heritability of SARS-CoV-2 susceptibility and COVID-19 severity","volume":"15","author":"KL Brown","year":"2024","journal-title":"Nat Commun"},{"issue":"11","key":"pgen.1012222.ref006","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1038\/s41588-021-00955-3","article-title":"Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus","volume":"53","author":"DJ Downes","year":"2021","journal-title":"Nat Genet"},{"key":"pgen.1012222.ref007","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.71235","article-title":"Regulatory dissection of the severe COVID-19 risk locus introgressed by Neanderthals","volume":"12","author":"E Jagoda","year":"2023","journal-title":"Elife"},{"key":"pgen.1012222.ref008","first-page":"1","article-title":"Identification and functional characterization of regulatory variants in DPP9 associated with COVID-19 severity","author":"G Farah","year":"2026","journal-title":"Genome Medicine"},{"issue":"6099","key":"pgen.1012222.ref009","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic localization of common disease-associated variation in regulatory DNA","volume":"337","author":"MT Maurano","year":"2012","journal-title":"Science"},{"issue":"9","key":"pgen.1012222.ref010","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1038\/s41588-019-0481-0","article-title":"A global overview of pleiotropy and genetic architecture in complex traits","volume":"51","author":"K Watanabe","year":"2019","journal-title":"Nat Genet"},{"issue":"11","key":"pgen.1012222.ref011","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1038\/s41588-023-01529-1","article-title":"Systematic differences in discovery of genetic effects on gene expression and complex traits","volume":"55","author":"H Mostafavi","year":"2023","journal-title":"Nat Genet"},{"key":"pgen.1012222.ref012","doi-asserted-by":"crossref","first-page":"102282","DOI":"10.1016\/j.gde.2024.102282","article-title":"Genetic factors mediating long-range enhancer-promoter communication in mammalian development","volume":"90","author":"G Bower","year":"2025","journal-title":"Curr Opin Genet Dev"},{"issue":"1","key":"pgen.1012222.ref013","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ajhg.2024.11.005","article-title":"Systematic functional characterization of non-coding regulatory SNPs associated with central obesity","volume":"112","author":"S-S Dong","year":"2025","journal-title":"Am J Hum Genet"},{"issue":"5","key":"pgen.1012222.ref014","article-title":"Massively parallel reporter assay investigates shared genetic variants of eight psychiatric disorders","volume":"188","author":"S Lee","year":"2025","journal-title":"Cell"},{"issue":"1","key":"pgen.1012222.ref015","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13073-025-01459-z","article-title":"Integration of functional genomics and statistical fine-mapping systematically characterizes adult-onset and childhood-onset asthma genetic associations","volume":"17","author":"X Zhong","year":"2025","journal-title":"Genome Med"},{"issue":"1","key":"pgen.1012222.ref016","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s41467-025-56725-w","article-title":"Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer","volume":"16","author":"C Chen","year":"2025","journal-title":"Nat Commun"},{"issue":"2","key":"pgen.1012222.ref017","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1161\/CIRCRESAHA.119.316006","article-title":"Identification of functional variant enhancers associated with atrial fibrillation","volume":"127","author":"AF van Ouwerkerk","year":"2020","journal-title":"Circ Res"},{"issue":"1","key":"pgen.1012222.ref018","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1038\/s41467-018-04451-x","article-title":"High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing","volume":"9","author":"P Zhang","year":"2018","journal-title":"Nat Commun"},{"issue":"6123","key":"pgen.1012222.ref019","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1126\/science.1232542","article-title":"Genome-wide quantitative enhancer activity maps identified by STARR-seq","volume":"339","author":"CD Arnold","year":"2013","journal-title":"Science"},{"issue":"5","key":"pgen.1012222.ref020","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.devcel.2021.02.016","article-title":"Enhancer grammar in development, evolution, and disease: dependencies and interplay","volume":"56","author":"GA Jindal","year":"2021","journal-title":"Dev Cell"},{"key":"pgen.1012222.ref021","article-title":"An expanded registry of candidate cis-regulatory elements","author":"JE Moore","year":"2026","journal-title":"Nature"},{"key":"pgen.1012222.ref022","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.cell.2016.09.018","article-title":"Ever-changing landscapes: transcriptional enhancers in development and evolution","volume":"167","author":"HK Long","year":"2016","journal-title":"Cell"},{"issue":"5","key":"pgen.1012222.ref023","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41579-022-00713-0","article-title":"SARS-CoV-2 pathogenesis","volume":"20","author":"MM Lamers","year":"2022","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"pgen.1012222.ref024","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1136\/thoraxjnl-2021-217561","article-title":"Respiratory epithelial cell responses to SARS-CoV-2 in COVID-19","volume":"77","author":"JP Bridges","year":"2022","journal-title":"Thorax"},{"issue":"6","key":"pgen.1012222.ref025","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1165\/rcmb.2012-0339OC","article-title":"Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus","volume":"48","author":"Z Qian","year":"2013","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"5","key":"pgen.1012222.ref026","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/jnci\/51.5.1417","article-title":"In vitro cultivation of human tumors: establishment of cell lines derived from a series of solid tumors","volume":"51","author":"DJ Giard","year":"1973","journal-title":"J Natl Cancer Inst"},{"key":"pgen.1012222.ref027","doi-asserted-by":"crossref","unstructured":"ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57\u201374.","DOI":"10.1038\/nature11247"},{"issue":"7848","key":"pgen.1012222.ref028","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-020-03065-y","article-title":"Genetic mechanisms of critical illness in COVID-19","volume":"591","author":"E Pairo-Castineira","year":"2020","journal-title":"Nature"},{"issue":"1","key":"pgen.1012222.ref029","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1038\/s41467-018-07607-x","article-title":"Human genome-wide measurement of drug-responsive regulatory activity","volume":"9","author":"GD Johnson","year":"2018","journal-title":"Nat Commun"},{"key":"pgen.1012222.ref030","doi-asserted-by":"crossref","DOI":"10.1002\/cpmb.105","article-title":"STARR-seq and UMI-STARR-seq: assessing enhancer activities for genome-wide-, high-, and low-complexity candidate libraries","volume":"128","author":"C Neumayr","year":"2019","journal-title":"Curr Protoc Mol Biol"},{"issue":"1","key":"pgen.1012222.ref031","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/jhg.2008.5","article-title":"The HLA genomic loci map: expression, interaction, diversity and disease","volume":"54","author":"T Shiina","year":"2009","journal-title":"J Hum Genet"},{"issue":"12","key":"pgen.1012222.ref032","doi-asserted-by":"crossref","first-page":"2210","DOI":"10.1016\/j.ajhg.2022.11.006","article-title":"Massively parallel reporter assays and variant scoring identified functional variants and target genes for melanoma loci and highlighted cell-type specificity","volume":"109","author":"E Long","year":"2022","journal-title":"Am J Hum Genet"},{"key":"pgen.1012222.ref033","article-title":"Functional dissection of complex trait variants at single-nucleotide resolution","author":"L Siraj","year":"2026","journal-title":"Nature"},{"issue":"18","key":"pgen.1012222.ref034","doi-asserted-by":"crossref","first-page":"13790","DOI":"10.3390\/ijms241813790","article-title":"rs71327024 Associated with COVID-19 hospitalization reduces CXCR6 promoter activity in human CD4+ T cells via disruption of c-Myb binding","volume":"24","author":"AN Uvarova","year":"2023","journal-title":"Int J Mol Sci"},{"key":"pgen.1012222.ref035","article-title":"Characterization of sequence determinants of enhancer function using natural genetic variation","volume":"11","author":"MG Yang","year":"2022","journal-title":"Elife"},{"issue":"7833","key":"pgen.1012222.ref036","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41586-020-2816-5","article-title":"Dense and pleiotropic regulatory information in a developmental enhancer","volume":"587","author":"T Fuqua","year":"2020","journal-title":"Nature"},{"issue":"4","key":"pgen.1012222.ref037","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.ajhg.2025.01.018","article-title":"An evolving understanding of multiple causal variants underlying genetic association signals","volume":"112","author":"E Long","year":"2025","journal-title":"Am J Hum Genet"},{"issue":"6586","key":"pgen.1012222.ref038","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1126\/science.abj5117","article-title":"Multiple causal variants underlie genetic associations in humans","volume":"375","author":"NS Abell","year":"2022","journal-title":"Science"},{"issue":"8099","key":"pgen.1012222.ref039","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41586-025-10014-0","article-title":"Advancing regulatory variant effect prediction with AlphaGenome","volume":"649","author":"\u017d Avsec","year":"2026","journal-title":"Nature"},{"issue":"8036","key":"pgen.1012222.ref040","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/s41586-024-08070-z","article-title":"Machine-guided design of cell-type-targeting cis-regulatory elements","volume":"634","author":"SJ Gosai","year":"2024","journal-title":"Nature"},{"issue":"4","key":"pgen.1012222.ref041","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.1074\/jbc.M009633200","article-title":"Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos\/Jun dimers","volume":"276","author":"T Ito","year":"2001","journal-title":"J Biol Chem"},{"issue":"7","key":"pgen.1012222.ref042","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/s41588-019-0455-2","article-title":"High-throughput identification of human SNPs affecting regulatory element activity","volume":"51","author":"J van Arensbergen","year":"2019","journal-title":"Nat Genet"},{"key":"pgen.1012222.ref043","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1502214","article-title":"FTO obesity variant circuitry and adipocyte browning in humans","volume":"373","author":"M Claussnitzer","year":"2015","journal-title":"N Engl J Med"},{"issue":"6546","key":"pgen.1012222.ref044","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1126\/science.abf1008","article-title":"Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5","volume":"372","author":"DR Sobreira","year":"2021","journal-title":"Science"},{"issue":"2","key":"pgen.1012222.ref045","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2016.09.005","article-title":"Enhancer variants synergistically drive dysfunction of a gene regulatory network in Hirschsprung disease","volume":"167","author":"S Chatterjee","year":"2016","journal-title":"Cell"},{"key":"pgen.1012222.ref046","doi-asserted-by":"crossref","first-page":"102416","DOI":"10.1016\/j.gde.2025.102416","article-title":"Enhancer cooperativity in the folded genome","volume":"96","author":"ET Friman","year":"2026","journal-title":"Curr Opin Genet Dev"},{"issue":"8065","key":"pgen.1012222.ref047","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41586-025-08844-z","article-title":"DNA-guided transcription factor interactions extend human gene regulatory code","volume":"641","author":"Z Xie","year":"2025","journal-title":"Nature"},{"issue":"3","key":"pgen.1012222.ref048","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1101\/gr.277246.122","article-title":"Enhancers display constrained sequence flexibility and context-specific modulation of motif function","volume":"33","author":"F Reiter","year":"2023","journal-title":"Genome Res"},{"issue":"3","key":"pgen.1012222.ref049","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nbt.2136","article-title":"Massively parallel functional dissection of mammalian enhancers in vivo","volume":"30","author":"RP Patwardhan","year":"2012","journal-title":"Nat Biotechnol"},{"issue":"10","key":"pgen.1012222.ref050","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.3390\/genes16101223","article-title":"Comparative analysis of deep learning models for predicting causative regulatory variants","volume":"16","author":"G Manzo","year":"2025","journal-title":"Genes (Basel)"},{"issue":"2","key":"pgen.1012222.ref051","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2025.10.029","article-title":"BRAIN-MAGNET: a functional genomics atlas for interpretation of non-coding variants","volume":"189","author":"R Deng","year":"2026","journal-title":"Cell"},{"key":"pgen.1012222.ref052","article-title":"Context-dependent regulatory variants in Alzheimer\u2019s disease","author":"Z Chen","year":"2025","journal-title":"bioRxiv"},{"key":"pgen.1012222.ref053","article-title":"ChromBPNet: bias factorized, base-resolution deep learning models of chromatin accessibility reveal cis-regulatory sequence syntax, transcription factor footprints and regulatory variants","author":"A Pampari","year":"2025","journal-title":"bioRxiv"},{"issue":"8054","key":"pgen.1012222.ref054","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41586-024-08430-9","article-title":"Massively parallel characterization of transcriptional regulatory elements","volume":"639","author":"V Agarwal","year":"2025","journal-title":"Nature"},{"key":"pgen.1012222.ref055","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.3389\/fimmu.2018.02589","article-title":"IFNAR2 is required for anti-influenza immunity and alters susceptibility to post-influenza bacterial superinfections","volume":"9","author":"KM Shepardson","year":"2018","journal-title":"Front Immunol"},{"issue":"5","key":"pgen.1012222.ref056","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/eji.202048793","article-title":"Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway","volume":"51","author":"I Meyts","year":"2021","journal-title":"Eur J Immunol"},{"key":"pgen.1012222.ref057","doi-asserted-by":"crossref","unstructured":"The ENCODE Project Consortium. Expanded encyclopaedias of DNA elements in the human and mouse genomes. Nature. 2020;583(7818):699\u2013710.","DOI":"10.1038\/s41586-020-2493-4"},{"issue":"2","key":"pgen.1012222.ref058","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/CCO.0000000000000713","article-title":"Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus","volume":"33","author":"CM Cardozo","year":"2021","journal-title":"Curr Opin Oncol"},{"issue":"5","key":"pgen.1012222.ref059","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1074\/jbc.M114.619890","article-title":"p53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling","volume":"290","author":"L Yuan","year":"2015","journal-title":"J Biol Chem"},{"key":"pgen.1012222.ref060","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.gene.2007.03.018","article-title":"Evolution of the interferon alpha gene family in eutherian mammals","volume":"397","author":"CH Woelk","year":"2007","journal-title":"Gene"},{"issue":"1","key":"pgen.1012222.ref061","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/s13059-021-02260-y","article-title":"LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions","volume":"22","author":"M Roller","year":"2021","journal-title":"Genome Biol"},{"issue":"8","key":"pgen.1012222.ref062","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1010436","article-title":"Mapping of promoter usage QTL using RNA-seq data reveals their contributions to complex traits","volume":"18","author":"N Kubota","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"pgen.1012222.ref063","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.41673","article-title":"Genetic effects on promoter usage are highly context-specific and contribute to complex traits","volume":"8","author":"K Alasoo","year":"2019","journal-title":"Elife"},{"issue":"4","key":"pgen.1012222.ref064","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1002\/jmv.26743","article-title":"Dysregulation of the mevalonate pathway during SARS-CoV-2 infection: an in silico study","volume":"93","author":"JL Gomez Marti","year":"2021","journal-title":"J Med Virol"},{"issue":"1","key":"pgen.1012222.ref065","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12915-025-02173-3","article-title":"Switching of OAS1 splicing isoforms overcomes SNP-derived vulnerability to SARS-CoV-2 infection","volume":"23","author":"K Iida","year":"2025","journal-title":"BMC Biol"},{"key":"pgen.1012222.ref066","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1471-2121-15-33","article-title":"Mitochondrial localization of the OAS1 p46 isoform associated with a common single nucleotide polymorphism","volume":"15","author":"KH Kj\u00e6r","year":"2014","journal-title":"BMC Cell Biol"},{"issue":"3","key":"pgen.1012222.ref067","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.humimm.2012.11.011","article-title":"Differential effects of a common splice site polymorphism on the generation of OAS1 variants in human bronchial epithelial cells","volume":"74","author":"S Noguchi","year":"2013","journal-title":"Hum Immunol"},{"issue":"6567","key":"pgen.1012222.ref068","doi-asserted-by":"crossref","DOI":"10.1126\/science.abj3624","article-title":"A prenylated dsRNA sensor protects against severe COVID-19","volume":"374","author":"A Wickenhagen","year":"2021","journal-title":"Science"},{"issue":"1","key":"pgen.1012222.ref069","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/path.4215","article-title":"Inhibition of BMP activity protects epithelial barrier function in lung injury","volume":"231","author":"T Helbing","year":"2013","journal-title":"J Pathol"},{"issue":"9","key":"pgen.1012222.ref070","article-title":"Niche-mediated BMP\/SMAD signaling regulates lung alveolar stem cell proliferation and differentiation","volume":"145","author":"M-I Chung","year":"2018","journal-title":"Development"},{"issue":"1","key":"pgen.1012222.ref071","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11882-024-01181-7","article-title":"Mechanisms of bone morphogenetic protein 2 in respiratory diseases","volume":"25","author":"Y Wen","year":"2024","journal-title":"Curr Allergy Asthma Rep"},{"issue":"1","key":"pgen.1012222.ref072","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2007.04.006","article-title":"Functional MAPT haplotypes: bridging the gap between genotype and neuropathology","volume":"27","author":"TM Caffrey","year":"2007","journal-title":"Neurobiol Dis"},{"issue":"13","key":"pgen.1012222.ref073","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1093\/hmg\/ddh149","article-title":"Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids","volume":"13","author":"KG Tantisira","year":"2004","journal-title":"Hum Mol Genet"},{"issue":"2","key":"pgen.1012222.ref074","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1440-1843.2008.01425.x","article-title":"Association between CRHR1 polymorphism and improved lung function in response to inhaled corticosteroid in patients with COPD","volume":"14","author":"WJ Kim","year":"2009","journal-title":"Respirology"},{"issue":"5","key":"pgen.1012222.ref075","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41390-018-0235-1","article-title":"Genetic variation in CRHR1 is associated with short-term respiratory response to corticosteroids in preterm infants at risk for bronchopulmonary dysplasia","volume":"85","author":"TOLSURF Study Group","year":"2019","journal-title":"Pediatr Res"},{"issue":"1","key":"pgen.1012222.ref076","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1038\/s41467-024-49756-2","article-title":"Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19","volume":"15","author":"UCSF COMET Consortium","year":"2024","journal-title":"Nat Commun"},{"issue":"6","key":"pgen.1012222.ref077","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1038\/ng.2609","article-title":"Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis","volume":"45","author":"TE Fingerlin","year":"2013","journal-title":"Nat Genet"},{"issue":"5","key":"pgen.1012222.ref078","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1164\/rccm.201905-1017OC","article-title":"Genome-wide association study of susceptibility to idiopathic pulmonary fibrosis","volume":"201","author":"RJ Allen","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"pgen.1012222.ref079","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0288138","article-title":"Tau protein aggregation associated with SARS-CoV-2 main protease","volume":"18","author":"RJ Eberle","year":"2023","journal-title":"PLoS One"},{"issue":"3","key":"pgen.1012222.ref080","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1101\/gr.276064.121","article-title":"Functional noncoding SNPs in human endothelial cells fine-map vascular trait associations","volume":"32","author":"A Toropainen","year":"2022","journal-title":"Genome Res"},{"issue":"11","key":"pgen.1012222.ref081","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/s41592-020-0965-y","article-title":"A systematic evaluation of the design and context dependencies of massively parallel reporter assays","volume":"17","author":"JC Klein","year":"2020","journal-title":"Nat Methods"},{"key":"pgen.1012222.ref082","doi-asserted-by":"crossref","first-page":"513535","DOI":"10.3389\/fgene.2020.00157","article-title":"LDlinkR: an R package for rapidly calculating linkage disequilibrium statistics in diverse populations","volume":"11","author":"TA Myers","year":"2020","journal-title":"Front Genet"},{"issue":"4","key":"pgen.1012222.ref083","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"B Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"2","key":"pgen.1012222.ref084","doi-asserted-by":"crossref","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"P Danecek","year":"2021","journal-title":"Gigascience"},{"issue":"3","key":"pgen.1012222.ref085","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1101\/gr.209601.116","article-title":"UMI-tools: modeling sequencing errors in Unique Molecular Identifiers to improve quantification accuracy","volume":"27","author":"T Smith","year":"2017","journal-title":"Genome Res"},{"issue":"2","key":"pgen.1012222.ref086","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq--a Python framework to work with high-throughput sequencing data","volume":"31","author":"S Anders","year":"2015","journal-title":"Bioinformatics"},{"issue":"12","key":"pgen.1012222.ref087","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"1","key":"pgen.1012222.ref088","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s12864-019-5556-x","article-title":"Linear models enable powerful differential activity analysis in massively parallel reporter assays","volume":"20","author":"L Myint","year":"2019","journal-title":"BMC Genomics"},{"issue":"2","key":"pgen.1012222.ref089","article-title":"voom: Precision weights unlock linear model analysis tools for RNA-seq read counts","volume":"15","author":"CW Law","year":"2014","journal-title":"Genome Biol"},{"issue":"4","key":"pgen.1012222.ref090","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"S Heinz","year":"2010","journal-title":"Mol Cell"},{"key":"pgen.1012222.ref091","author":"A Shrikumar","year":"2018"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1012222","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:58:57Z","timestamp":1784915937000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012222"}},"subtitle":[],"editor":[{"given":"Anne","family":"Goriely","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":91,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1012222","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}