{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE281237"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Widespread gene-environment interactions shape the immune response to SARS-CoV-2 infection","description":"Genome-wide association studies performed in COVID-19 patients have uncovered various loci significantly associated with susceptibility to SARS-CoV-2 infection and disease severity. However, the underlying cis-regulatory genetic factors contributing to heterogeneity in the response to SARS-CoV-2 infection and their impact on clinical phenotypes remain enigmatic. Here, we use single-cell RNA-sequencing to quantify genetic contributions to cis-regulatory variation in 361,119 peripheral blood mononuclear cells of 63 acute COVID-19 patients, 39 convalescent samples, and 106 healthy controls. Expression quantitative trait loci mapping across cell types within each disease state group reveals thousands of cis-associated variants, of which hundreds are detected exclusively in immune cells derived from acute patients. Patient-specific genetic effects dissipate as infection resolves, suggesting that distinct gene regulatory networks are at play in the active infection state. Further, 20.3% of tested loci demonstrate significant cell state interactions with genotype, with pathways related to interferon responses and oxidative phosphorylation showing pronounced cell state-dependent variation, predominantly in CD14+ monocytes. Overall, we estimate that 16.8% of tested genes exhibit gene-environment interaction effects, highlighting the importance of environmental modifiers in the transcriptional regulation of the immune response to SARS-CoV-2. Our findings argue for the existence of extensive gene-environment effects among patients responding to an infection.","dates":{"publication":"2026/04/01"},"accession":"GSE281237","cross_references":{"GSM":["GSM8615469","GSM8615467","GSM8615489","GSM8615468","GSM8615487","GSM8615465","GSM8615466","GSM8615488","GSM8615485","GSM8615464","GSM8615486","GSM8615483","GSM8615484","GSM8615481","GSM8615482","GSM8615480","GSM8615478","GSM8615479","GSM8615476","GSM8615477","GSM8615474","GSM8615475","GSM8615472","GSM8615473","GSM8615470","GSM8615492","GSM8615471","GSM8615490","GSM8615491"],"GPL":["24676"],"GSE":["281237"],"taxon":["Homo sapiens"]}}