{"doi":"10.5281/zenodo.7270242","title":"Altered and allele-specific open chromatin landscape reveals epigenetic and genetic regulators of innate immunity in COVID-19","abstract":"While SARS-CoV-2 infection causes mild respiratory disease in most individuals, a small group of patients develops severe COVID-19. Dysfunctional innate immune responses have been identified to contribute to differences in COVID-19 severity, but the key regulators are still unknown. Here, we present an integrative single-cell epigenetics, transcriptomic, and genetics analysis of peripheral blood mononuclear cells from hospitalized and convalescent COVID-19 patients. In classical monocytes, we identified 41.3% of significantly up-regulated genes in hospitalized COVID-19 patients potentially induced by differential chromatin accessibility. Sub-clustering and motif-enrichment analyses of monocytes reveal disease condition-specific regulation by transcription factors, such as <em>C/EBPs</em> and <em>SPI1</em>, and their targets, including a long-noncoding RNA <em>LUCAT1</em>, which further regulates interferon responses and is associated with the need for oxygen supply of COVID-19 patients. The interaction between <em>C/EBPs</em> and <em>LUCAT1</em> was validated through loss-of-function experiments. Finally, we investigated genetic risk variants that exhibit allele-specific open chromatin (ASoC) in promoters/enhancers of COVID-19 patients. Integrating our data with publicly available expression quantitative trait loci and chromosomal interactions indicates that ASoC SNP rs6800484-C is associated with lower expression of <em>CCR2</em>, which may contribute to higher viral loads in the lungs and a higher risk of COVID-19 hospitalization. Altogether, our study highlights the diverse genetic and epigenetic regulators that contribute to the innate immune responses of different COVID-19 patients.","journal":"MDC Repository (Max-Delbrueck-Center for Molecular Medicine)","year":2022,"id":294028,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9334,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":775013,"name":"Zhenhua Zhang","orcid":"0000-0003-0711-7466","position":1,"is_corresponding":false},{"id":406363,"name":"Valerie A. C. M. Koeken","orcid":"0000-0002-5783-9013","position":2,"is_corresponding":false},{"id":890415,"name":"Saumya Kumar","orcid":"0000-0001-9481-1944","position":3,"is_corresponding":false},{"id":891003,"name":"Michelle Aillaud","orcid":null,"position":4,"is_corresponding":false},{"id":891004,"name":"Hsin-Chieh Tsay","orcid":null,"position":5,"is_corresponding":false},{"id":890416,"name":"Zhaoli Liu","orcid":"0000-0002-3641-4470","position":6,"is_corresponding":false},{"id":979417,"name":"Ane R. M. Kraft","orcid":null,"position":7,"is_corresponding":false},{"id":890418,"name":"Chai Fen Soon","orcid":"0000-0003-0929-4263","position":8,"is_corresponding":false},{"id":890419,"name":"Ivan Odak","orcid":"0000-0003-0408-5091","position":9,"is_corresponding":false},{"id":979418,"name":"Berislay Bosnjak","orcid":null,"position":10,"is_corresponding":false},{"id":979419,"name":"Anna Volt","orcid":null,"position":11,"is_corresponding":false},{"id":979420,"name":"Deutsche COVID- OMICS Initiative","orcid":null,"position":12,"is_corresponding":false},{"id":271335,"name":"Morris A. Swertz","orcid":"0000-0002-0979-3401","position":13,"is_corresponding":false},{"id":28491,"name":"Uwe Ohler","orcid":"0000-0002-0881-3116","position":14,"is_corresponding":false},{"id":57957,"name":"Robert Geffers","orcid":"0000-0003-4409-016X","position":15,"is_corresponding":false},{"id":2344,"name":"Thomas Illig","orcid":"0000-0003-4284-5389","position":16,"is_corresponding":false},{"id":863527,"name":"Jochen Huehn","orcid":"0000-0001-8071-1379","position":17,"is_corresponding":false},{"id":28524,"name":"Antoine‐Emmanuel Saliba","orcid":"0000-0001-8539-2784","position":18,"is_corresponding":false},{"id":28501,"name":"Leif Erik Sander","orcid":"0000-0002-0476-9947","position":19,"is_corresponding":false},{"id":706647,"name":"Reinhold Förster","orcid":"0000-0001-6190-7923","position":20,"is_corresponding":false},{"id":281747,"name":"Cheng‐Jian Xu","orcid":"0000-0003-1586-4672","position":21,"is_corresponding":false},{"id":74483,"name":"Markus Cornberg","orcid":"0000-0002-9141-8001","position":22,"is_corresponding":false},{"id":710429,"name":"Leon N. 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